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PHARMACOKINETICS OF CEFTRIAXONE IN NORMAL AND

SALMONELLA TYPHIMURIM INFECTED GOATS

Mossad Gamal El-Din EL Sayed-Ashraf Abd El ndashHakim ElndashKomy Faten Ibrahim EL

Sayed

Faculty of Veterinary Medicine Benha University Egypt Department of Pharmacology

ABSTRACT

The pharmacokinetic parameters of ceftriaxone in blood urine and

milk following intravenous and intramuscular (single amp repeated)

administrations were estimated in normal and experimentally

Salmonella typhimurum infected goats Following a single intravenous

injection of 20 mg ceftriaxonekg bwt in normal goats ceftriaxone

could be detected therapeutically for 8 hours post intravenous

injection The serum concentration ndash time curve of ceftriaxone

following intravenous injection showed that the drug obeyed a two

compartments open model The intramuscular bioavailability of

ceftriaxone in normal goats was 6128 Intramuscular injection of 20

mg ceftriaxone per kilogram body weight twice daily for five

consecutive days in normal and Salmonella typhimurium infected

goats revealed a lower significant serum ceftriaxone concentration after the first third fifth

seventh ninth doses in Salmonella typhimurium infected goats compared with normal goats

The high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular

administrations suggested that ceftriaxone could be used for treatment of mastitis caused by

Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats

The high concentrations of ceftriaxone in urine after repeated intramuscular administrations

suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections

caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in

goats

KEYWORDS Pharmacokinetics ceftriaxone goats

WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

SJIF Impact Factor 5210

Volume 5 Issue 02 1433-1458 Research Article ISSN 2278 ndash 4357

Correspondence for

Author

Dr Faten Ibrahim EL

Sayed

Faculty of veterinary

medicine Benha

University Egypt

Department of

Pharmacology

Article Received on

19 Dec 2015

Revised on 09 Jan 2016

Accepted on 29 Jan 2016

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INTRODUCTION

Ceftriaxone is a third-generation semi-synthetic bactericidal cephalosporin antibiotic

resistant to various types of bacterial β-lactamases It has excellent activity against gram

negative bacteria as well as a wide range of gram-positive and some anaerobic bacteria

including enterobacteriaceae Streptococcus pneumoniae Haemophilus inflfl uenzae

Pseudomonas aeruginosa and other non-enterococcal streptococci[123]

Like other

cephalosporin ceftriaxone bind to the penicillin-binding proteins (PBP) by covalent bond and

inactivate transpeptidase enzymes thereby inhibiting the peptidoglycan synthesis leading to

inhibition of the cell wall synthesis[4]

It has rapid absorption and wide distribution in tissues

as well as body fluids after parenteral administration in animals[5]

The drug thus seems to be

useful in the treatment of a variety of bacterial infections including meningitis septicemia

pyoderma colibacillosis surgical prophylaxis and urinary tract respiratory tract wound soft

tissue and joint infections[2]

Clinical pharmacology of ceftriaxone was investigated in human[6]

sheep[78]

goats[91011]

buffulo calves[1213]

calves[14]

domestic cats[15]

cross bred cow calves[16]

Little literature was

found concerning the pharmacokinetics of ceftriaxone in goats Thus the aim of present

work was undertaken to study the pharmacokinetic parameters of ceftriaxone after

intravenous and intramuscular injection in normal and experimentally Salmonella

typhimurium infected goats also the bioavailability of ceftriaxone was calculated after a

single intramuscular injection in normal goats

MATERIAL AND METHODS

Drug

Ceftriaxone is a member of third generation cephalosporins ceftriaxone sodium was used in

this study under the trade name (Cefaxonereg) It is available as glass vial containing 1000 mg

ceftriaxone it was produced by Pharco company Egypt

Experimental animals

Four clinically normal lactating baladi four experimentally infected goats and lactating goats

were used for each drug in this investigation The body weight and age of the tested goats

ranged from 20-26 kg and from 2 to 3 years old (for normal goats) and from 22 ndash 29 kg and

from 25 to 35 years old for experimentally infected goats They were housed in hygienic

stable fed on barseem drawa and concentrate Water was provided ad-libitum

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Grouping of goats

Group (1)

It included 4 normal post-partum lactating goats Each goat was injected intravenously into

the left jugular vein ceftriaxone These goats were left for 15 days after the intravenous

injection to insure complete excretion of ceftriaxone from bodies of goats Then each goat

was injected intramuscularly into the gluteus medius muscle with the same dose of

ceftriaxone The aim of intramuscular injection to calculate the bioavailability of ceftriaxone

in normal goats

Group (2)

It included 4 normal post-partum lactating goats Each goat was injected intramuscularly into

the gluteus medius muscle with 20 mgkg bwt ceftriaxone for five consecutive days

Group (3)

It included 4 experimentally infected post-partum lactating goats with twenty four hours

peptone water culture of enterpathogen Salmonella typhimurium which were cultured on

nutrient agar plates for 24 hours then suspension of culture were collected by sterile saline

By opacity tube the required concentration of 2Χ109 micro-organismsml was obtained Each

of the four goats received orally a 10 ml suspension containing 2x109

organismml The

clinical symptoms of bacteraemia as fever and diarrhea appeared after 48-72 hours of

injection with Salmonella typhimurium suspension[17]

Each goat was injected

intramuscularly into the gluteus medius muscle with ceftriaxone per kilogram body weight

48 hours after experimental infection with samlonella Typhmurium for five consecutive days

Collection of samples

Blood samples

Blood samples were collected from right jugular vein following a single intravenous injection

of ceftriaxone in normal goats blood samples were collected after 5 min 10 min15 min 30

min 1 2 4 8 and 12 hours of administration Blood samples following the second third

fourth and fifth intramuscular doses were collected before and 10 min 15 min 050 1 2 4 8

and 12 hours post injection Blood samples taken from goats were allowed to clot and the

serum separated by centrifugation collected and divided in to two parts the first part was

used for assay of ceftriaxone and the second part was used for creatinine assay All serum

samples were stored at ndash 20degC until assay for ceftriaxone and creatinine

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Urine samples

The urine sample was taken by using rubber balloon catheter (Folatex No 4158512) The

goats were catheterized and bladder was evacuated before each experiment Following

injection of ceftriaxone (single intravenous single intramuscular and repeated intramuscular

administration) in goats (normal and experimentally infected) urine samples were taken after

025 050 1 2 4 8 12 24 and 48 hours of administrations Urine sample which was taken

at 025 h was discarded Urine samples from goats of group (1) group (2) group (3) were

collected and divided into two parts the first part was used for assay of ceftriaxone and the

second part was used for creatinine assay All urine samples were stored at - 20degC until assay

for ceftriaxone After the end of each experiment the urinary bladder was irrigated with 15

milliliters potassium permanganate solution 1 5000 as antiseptic agent

Milk samples

The udder was completely evacuated before drug administration and milk samples were

collected by hand stripping from both teats Following injection of ceftriaxone (single

intravenous single intramuscular and repeated intramuscular administration) in goats (normal

and experimentally infected) milk samples were taken after 050 1 2 4 8 12 24 and 48

hours of administrations Milk sample which was taken at 025 h was discarded The udder of

each goat in all groups was completely evacuated before drug administration and after each

milk samples Milk samples from goats of all groups were allowed to clot (by mixing equal

volumes of milk and 25 trichloroacetic acid) and centrifuged The skim milk was collected

and stored at ndash 20degC until assay for ceftriaxone

Analytical Procedure

Assay of ceftriaxone

Ceftriaxone was assayed in goats serum distalled water and goats milk by microbiological

method using agar well diffusion method by using of Escherichia coli ATCC (American

type culture collection 25922) as tested microorganism which was obtained from

Microbiological Department Animal Health Institute Doky Giza Egypt)[18]

Concentrations of ceftriaxone in biological fluids were determined by modification of the

agar ndash plate diffusion method[19]

using Escherichia coli ATCC25922 as assay organism and

Muller Hinton agar media

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Assay of samples

According to[20]

three plates were used for each sample Six pores were made three of them

were filled with reference concentration while the other three pores were filled with the

serum milk or urine samples in triplicate manner The plates were incubated at 37degC for 18

hours then the diameter of inhibitory zones were measured The diameter of inhibitory zones

of samples were corrected by using the zone diameter of the reference concentration in the

same manner as previously discussed either by addition or subtraction From the standard

curve the concentrations corresponding to the corrected values of the inhibitory zones were

obtained

Drug clearance

Clearance of the tested drug from the blood of goats was estimated according to the following

equation

Drug clearance10 kg b wt =

Drug concentration in urine (microgml) X rate of diuresis (mlmin) Body weight (Kg)

_________________________________________________________________

Drug concentration in serum (microgml) X 10

Assay of creatinine in serum and urine

Creatinine was assayed by[21]

and performed by kit manufactured by Diamond diagnostics

company

Creatinine clearance

The creatinine clearance (mlmin10 kgbwt) for goats was calculated by the following

equation

Creatinine clearance 10 kgbwt =

Creatinine concentration in urine (mgL) X rate of diuresis (mlmin) Body weight (Kg)

______________________________________________________________________

Creatinine concentration in serum (mgL) X 10

Pharmacokinetic analysis

The pharmacokinetic parameters were calculated by using Winonlin version 12 and other

parameters according to[2223]

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Statistical Analysis

The data were calculated as mean plusmn standard error All statistical analysis were carried out

according to[24]

using the scientific calculator CASIO fx 120

RESULTS

Following a single intravenous injection of 20 mg ceftriaxonekg bwt in normal goats

ceftriaxone could be detected therapeutically for 8 hours post intravenous injection The

serum concentration ndash time curve of ceftriaxone following intravenous injection showed that

the drug obeyed a two compartments open model (Figure 1) The disposition kinetics of

ceftriaxone following a single intravenous intramuscular injection were recorded in table (1)

Intramuscular injection of 20 mg ceftriaxone per kilogram body weight twice daily for five

consecutive days in normal and Salmonella typhimurium infected goats revealed a lower

significant serum ceftriaxone concentration after the first third fifth seventh ninth doses in

Salmonella typhimurium infected goats compared with normal goats The pharmacokinetic

parameters of ceftriaxone after repeated intramuscular injection in normal were compared to

those in Salmonella typhimurium infected goats (Table 2) and (Figure 2 amp 3)

The highest concentrations of ceftriaxone in milk were recorded 4 hours after each

intramuscular dose (Table 3) with a significant lower value in Salmonella typhimurium

infected goats compared with normal goats The calculated milkserum concentrations ratios

of ceftriaxone after repeated intramuscular injection (Table 4)

The amount of urine (mlmin) voided after repeated intramuscular injection of 20 mgkg bwt

Twice daily of ceftriaxone for five consecutive days in normal and experimentally

Salmonella typhimurium infected goats were recorded in table (5) The mean peak urine

concentrations of ceftriaxone (Table 6) were reached 2 hours after each intramuscular dose

with a lower significant concentration in Salmonella typhimurium infected goats compared

with normal goats Urineserum concentration ratios of ceftriaxone after repeated

intramuscular injection in normal and experimentally Salmonella typhimurium infected goats

were calculated and illustrated in table (7) Creatinine clearance (mlmin10 kg bwt)

expressing glomerular filtration rate from blood of goats was shown in table (8) The rate of

ceftriaxone clearance (mlmin10 kg bwt) from blood of goats was shown in table (9) The

ratio between ceftriaxone clearance and creatinine clearance was calculated and illustrated in

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

table (10) The data revealed a significant lower ratio in Salmonella typhimurium infected

goats compared with normal goats after the third fifth seventh ninth doses

Table (1) Pharmacokinetics parameters of ceftriaxone (μgml) following a single

intravenous and intramuscuer injection of 20 mgkg bwt in normal goats (n=4)

Intramusculer_

(XplusmnS E)

Intravenous_

(XplusmnS E) Unit Parameters

-------- 1213 plusmn321321 microgml Cdeg

4360plusmn12343 61390 plusmn330 microgml A

43440plusmn43660 636 plusmn43316 h-1

α

43433plusmn3340 43340 plusmn43442 H (α) 43 T

43420plusmn43233 4333plusmn131 h-1

K12

43446plusmn43400 43409plusmn231 h-1

K21

-------- 43440plusmn431 lkg Vdss

4321plusmn6340 43636plusmn1303 microgml B

434446plusmn43419 43443plusmn43136 h-1

β

43141plusmn39340 43411plusmn331 H t05(β))

4344plusmn43401 434440plusmn43409 lkgh Cl tot

-------- 1136plusmn2111300 microgmlh AUMC

-------- 43303 plusmn0314 H MRT

9300plusmn2439 30plusmn034330 microgmlh AUC

3392plusmn63329 -------- F

43436plusmn4361 -------- h-1

K01

43420plusmn3346 -------- h-1

T05(k01)

4342plusmn330 -------- H Tmax(calc))

43021plusmn04343 -------- μgml Cmax(calc)

Cdeg Drug concentration in the serum at zero time immediately after a single intravenous

injection (μgml) A amp B Zero time plasma drug concentration intercepts of biphasic

intravenous disposition curve The coefficient B is based on the terminal exponential phase

(μgml) α amp β Hybrid rate constant of biphasic intravenous disposition curve values of α

and β are related to the slopes of distribution and elimination phase respectively of

biexponential drug disposition curve (h-1

) T05 (α) Distribution half ndash life (h) t05 (β)

Elimination half ndash life (h) K12 First ndash order transfer rate constant for drug distribution from

Central to peripheral compartment (h-1

) K21 First order transfer rate constant for drug

distribution from Peripheral to central compartment (h-1

) Vdss The apparent volume of

distribution which was calculated by steady ndash state method (mlkg) AUMC Area under

moment curve MRT Mean residence time AUC Total area under the serum drug

concentration versus time curve from t = 0 to t = α after administration of a single dose F

Bioavailability Cmax maximum drug concentration Tmax time of maximum observed

concentration in blood

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Figure (1) Arthimatic plot of Serum concentrations of ceftriaxone (μgml) in normal

goats following a single intramuscular injection )diamsdiams( previously given the same doseby

a single intravenous injection () of 20 mg ceftriaxonekgbwt (n=4)

Figure (2) Semilogarthmic graph depicting the time course of ceftriaxone in serum of

normal goats following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt

twice dialy for five consecutive days (n=4)

Figure (3) Semilogarthmic graph depicting the time course of ceftriaxone in serum of

experimentally Salmonella typhimurim infected goats following repeated ntramuscular

injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4) 3

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Table (2) Pharmacokinetic parameters of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected

goats following repeated ntramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)

Dose

Unit

عىهParameters

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1269plusmn0073 7409plusmn121 1352plusmn0132 6373plusmn147 1410plusmn0243 5923plusmn126 1461plusmn0214 5430plusmn125 1424plusmn0172 7635plusmn176 gmlmicro A

0651plusmn0049 plusmn000843116 0720plusmn0008 plusmn00413300 0823plusmn0006 plusmn00263322 0848plusmn0025 plusmn00233323 0786plusmn0028 133plusmn0033 h-1 Α

106plusmn0008 330plusmn0015 0962plusmn0011 0392plusmn0007 0841plusmn0007 0567plusmn012 0818plusmn0024 0569plusmn0012 0885plusmn0030 plusmn00124322 H T05(α)

248plusmn0019 168plusmn0047 203plusmn0075 181plusmn0033 267plusmn0039 120plusmn0028 248plusmn0060 122plusmn0026 222plusmn0100 136plusmn0027 h-1 Kab

0278plusmn0002 0412plusmn0009 0342plusmn0012 0383plusmn0008 0252plusmn0009 0567plusmn0011 0279plusmn0005 00569plusmn0011 0314plusmn0014 0 510plusmn0012 H T05(ab)

0627plusmn0008 0378plusmn0007 0430plusmn0008 0402plusmn0008 0113plusmn00027 0424plusmn0009 0117plusmn0004 0394plusmn0008 0116plusmn0003 0239plusmn0005 h-1 K12

121plusmn0013 0962plusmn0022 141plusmn0021 130plusmn0023 0666plusmn0019 0651plusmn0013 0683plusmn0020 0660plusmn0013 0761plusmn0039 0998plusmn0023 h-1 K21

115plusmn0035 129plusmn0026 104plusmn0047 112plusmn0024 106plusmn0037 122plusmn0025 110plusmn0077 119plusmn0023 0910plusmn0032 123plusmn0023 H Tmax

4182plusmn0628 6108plusmn140 3440plusmn0363 5135plusmn0860 3117plusmn0965 4774plusmn0854 2713plusmn0781 4243plusmn0 870 2479plusmn0547 4065plusmn0825 gmlmicro Cmax

4944plusmn0820 7195plusmn142 4199plusmn0702 6511plusmn130 3190plusmn0688 5117plusmn113 3185plusmn0909 4709plusmn0990 3256plusmn0918 6329plusmn139 gmlmicro B

0164plusmn0003 0189plusmn00043 0181plusmn0002 0178plusmn0004 0181plusmn00035 0167plusmn0004 0214plusmn0009 0195plusmn0005 0249plusmn0918 0272plusmn0006 h-1 β

423plusmn0079 367plusmn0086 381plusmn0047 388plusmn0089 382plusmn0074 415plusmn0081 325plusmn0139 355plusmn0075 277plusmn0056 255plusmn0050 H T05β

0879plusmn0015 0429plusmn0009 109plusmn0004 0426plusmn0009 133plusmn0022 0503plusmn0011 154plusmn0064 0675plusmn0013 171plusmn0060 0693plusmn0014 Lkgh Cltot

28358plusmn215 40775plusmn808 21784plusmn0888 34259plusmn720 17860plusmn155 30705plusmn601 15281plusmn239 24135plusmn555 12175plusmn144 20292plusmn487 gmlhmicro AUC

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (3) Milk concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats

following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)

Dose Time of

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

197plusmn0205 200plusmn0408 125plusmn0104 155plusmn0132 0887plusmn0013 0885plusmn014 0500plusmn0040 074plusmn0012 ------------ ------ Before

200plusmn0408 22plusmn0108 197plusmn0205 200plusmn0408 155plusmn0132 197plusmn0205 100plusmn000 155plusmn0132 ----------- -------- 050

526plusmn0166 700plusmn0408 300plusmn0408 64plusmn0163 25plusmn0204 600plusmn0408 155plusmn0132 582plusmn0118 100plusmn000 520plusmn0166 1

640plusmn0163 900plusmn0408 582plusmn0118 792plusmn0114 582plusmn0118 755plusmn0221 275plusmn0061 700plusmn0408 200plusmn0408 691plusmn0176 2

900plusmn0408 1512plusmn0125 640plusmn0163 1475plusmn0322 640plusmn0163 1400plusmn0408 600plusmn0408 1352plusmn0205 526plusmn166 1225plusmn0595 4

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

350plusmn0353 400plusmn0408 300plusmn0408 392plusmn0125 300plusmn0408 35plusmn0353 275plusmn006 300plusmn0408 155plusmn0132 275plusmn0061 6

300 plusmn0408 35plusmn0353 125plusmn0104 200plusmn0408 125plusmn0104 155plusmn01 0825plusmn0062 100plusmn000 0500plusmn0040 0887plusmn0013 8

200plusmn0408 22plusmn0108 100plusmn000 155plusmn0132 100plusmn000 125plusmn0104 0730plusmn002 0825plusmn0078 0422plusmn000 073plusmn0020 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (4) Milkserum concentrations ratios of ceftriaxone in normal and experimentally Salmonella typhimurim infected

goats following repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice daily for five consecutive days (n=4)

Dose Time of

a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

0400plusmn0049 025plusmn0063 0307plusmn0026 021plusmn0019 0365plusmn00064 016plusmn0026 0232plusmn0016 0205plusmn0002 -------- helliphelliphelliphellip Before

0057plusmn0125 0042plusmn00025 0062plusmn00062 0042plusmn0010 0575plusmn00062 0055plusmn0006 0067plusmn0016 0049plusmn0005 --------- -------- 050

0127plusmn00062 0115plusmn00064 008plusmn0012 0117plusmn0004 0088plusmn00054 0122plusmn0008 008plusmn0017 0126plusmn0028 0039plusmn0005 0122plusmn0004 1

018plusmn0008 0185plusmn0010 021plusmn0004 017plusmn0004 0182plusmn0054 0179plusmn0006 0112plusmn00025 0193plusmn0012 0097plusmn0020 019plusmn0004 2

0357plusmn0020 0425plusmn0005 033plusmn0021 045plusmn0009 0285plusmn0082 0494plusmn0015 0395plusmn0016 0572plusmn001 0415plusmn0017 054plusmn0027 4

018plusmn0015 016plusmn0016 0207plusmn0022 0175plusmn0006 0257plusmn0037 0180plusmn0017 0272plusmn0015 0201plusmn003 0196plusmn0016 0222plusmn0002 6

0212plusmn0033 0212plusmn0020 0200plusmn0044 0122plusmn0024 0152plusmn0011 014plusmn0022 0122plusmn00062 0102plusmn0001 0107plusmn00094 0117plusmn0002 8

0372plusmn0042 025plusmn001 0325plusmn0027 0192plusmn0014 0265plusmn00064 0185plusmn0015 0272plusmn0125 0195plusmn0012 0252plusmn0032 0275plusmn0009 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

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Table (5) The amount of urine (mlmin) voided in normal and experimentally Salmonella typhimurim infected goats following

repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)

Dose Time of a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

plusmn00372344 126plusmn0034 130plusmn0030 130plusmn0028 118plusmn0066 118plusmn0067 108plusmn0013 108plusmn0008 ----------- -------- Before

0577plusmn0069 43494057plusmn 045plusmn0060 plusmn0064309 0312plusmn002 033plusmn0012 0340plusmn0024 033plusmn0012 0287plusmn0017 0272plusmn0014 050

0712plusmn0019 0692plusmn0014 068plusmn0081 0697plusmn0006 0672plusmn0011 0675plusmn 0009 0635plusmn0032 0655plusmn0010 0719plusmn0031 0697plusmn0015 1

0837plusmn0025 0787plusmn0021 0732plusmn0011 plusmn00054300 0715plusmn0011 0715plusmn002 0722plusmn0019 0702plusmn0018 0737plusmn0027 0762plusmn0041 2

0535plusmn0095 0507plusmn0021 0447plusmn0022 0452plusmn002 0402plusmn0075 0405plusmn0011 0400plusmn0057 0397plusmn0009 0380plusmn0004 038plusmn001 4

0437plusmn00094 0432plusmn0008 0400plusmn0010 0405plusmn0002 0380plusmn0007 plusmn00044319 0372plusmn0047 037plusmn 0007 0350plusmn0005 0365plusmn0006 6

0397plusmn0028 0410plusmn0008 0380plusmn0012 0395plusmn0009 0355plusmn0086 0352plusmn0007 0340plusmn0004 0345plusmn0005 0302plusmn0004 0335plusmn0005 8

0385plusmn001 0380plusmn0010 0385plusmn00064 0380plusmn0008 0365plusmn0064 0367plusmn0004 0362plusmn0086 0372plusmn0106 0327plusmn0006 0362plusmn0016 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (6) Urine concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats

following repeated intramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)

Dose Time of a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1125plusmn150 1125plusmn15 735plusmn287 81plusmn324 183plusmn03 555plusmn798 37plusmn0811 1815plusmn43290 -------------- ------ Before

2415plusmn357 2625plusmn374 1695plusmn788 249plusmn574 10575plusmn64 2415plusmn357 5400plusmn273 2085plusmn991 102plusmn160 168plusmn547 050

26025plusmn787 2923plusmn479 22425plusmn1225 2805plusmn35 1695plusmn618 2705plusmn471 10200plusmn547 2415plusmn357 6975plusmn225 22425plusmn894 1

29295plusmn765 3012plusmn346 28575plusmn738 2964plusmn415 2355plusmn259 2923plusmn479 1635plusmn561 2645plusmn917 102plusmn547 24825plusmn616 2

23475plusmn430 2482plusmn616 23475plusmn1564 2415plusmn357 1695plusmn788 198plusmn848 8475plusmn309 1515plusmn708 60plusmn212 1185plusmn45 4

1905plusmn45 2355plusmn259 153plusmn519 1935plusmn960 114plusmn948 159plusmn173 6675plusmn309 1215plusmn45 1312plusmn0552 855plusmn193 6

153plusmn1024 1965plusmn135 1335plusmn1229 150plusmn34 735plusmn295 1365plusmn665 6181plusmn339 72plusmn244 907plusmn0951 5025plusmn143 8

135plusmn519 120plusmn346 11725plusmn1551 96plusmn874 525plusmn295 75plusmn173 153plusmn130 39plusmn212 3735plusmn0458 13125plusmn0552 12

Between normal and diseased

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Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (7) Urineserum concentrations ratios of ceftriaxone following repeated ntramuscular injection of 20 mg

ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats

(n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

229plusmn 163 1448plusmn0743 1885plusmn159 1125plusmn0484 533plusmn0260 1050plusmn358 175plusmn0380 4146plusmn116 ------- ------ Before

741plusmn0063 plusmn01553 58plusmn0242 plusmn0149390 422plusmn0206 683plusmn0106 245plusmn0092 667plusmn0306 0510plusmn0081 559plusmn0181 050

651plusmn0243 plusmn0065031 637plusmn0373 plusmn014431 565plusmn0243 plusmn0085300 360plusmn0303 plusmn0110312 279plusmn0121 534plusmn0248 1

836plusmn0150 plusmn00476322 862plusmn0180 plusmn010463 942plusmn0166 plusmn0130631 217plusmn0303 727plusmn0256 508plusmn0186 plusmn01680340 2

939plusmn0235 plusmn01580344 1006plusmn0710 plusmn00750310 999plusmn0542 plusmn02850344 565plusmn0223 641plusmn0241 48plusmn0164 plusmn014834 4

1005plusmn0418 2plusmn018813 1097plusmn0641 plusmn03979300 993plusmn0921 plusmn0252931 619plusmn0483 plusmn0362933 167plusmn0101 642plusmn0644 6

1091plusmn0649 plusmn075332339 1171plusmn0980 995plusmn0415 925plusmn0593 plusmn05593433 886plusmn0408 plusmn02510311 2055plusmn0311 plusmn02046310 8

2392plusmn129 plusmn032731396 1794plusmn0228 1222plusmn124 1418plusmn109 plusmn026733336 580plusmn0397 plusmn03951326 227plusmn0452 plusmn02740316 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (8) Creatinine clearance (mlmin10kgbwt) following repeated intramuscular injection of 20 mg ceftriaxonekgbwt

twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats (n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1115plusmn0703 2265plusmn167 481plusmn0409 672plusmn0817 669plusmn0672 1202plusmn0777 695plusmn0634 1724plusmn179 ----------- ------ Before

0703plusmn0091 147plusmn0305 0718plusmn0141 251plusmn0707 0547plusmn0055 0699plusmn0092 0802plusmn0099 103plusmn0106 295plusmn0124 0458plusmn0037 050

101plusmn0075 161plusmn0093 131plusmn0099 264plusmn0217 161plusmn0146 373plusmn0499 247plusmn0110 4755plusmn0582 214plusmn0234 103plusmn0166 1

157plusmn0198 387plusmn0340 173plusmn0501 267plusmn0217 187plusmn0563 287plusmn0499 451plusmn0223 972plusmn105 263plusmn0399 169plusmn0454 2

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

184plusmn0095 346plusmn0444 173plusmn0501 436plusmn0599 383plusmn0299 682plusmn0584 328plusmn0253 119plusmn153 123plusmn0057 292plusmn0742 4

221plusmn0242 411plusmn0661 241plusmn0186 663plusmn0584 308plusmn0234 422plusmn0314 353plusmn0393 548plusmn0901 105plusmn0057 264plusmn0294 6

261plusmn0295 476plusmn0339 319plusmn0273 753plusmn0676 106plusmn0207 0773plusmn0049 228plusmn0175 456plusmn0340 206plusmn0160 404plusmn0419 8

310plusmn0218 409plusmn0434 3264plusmn0153 669plusmn0476 209plusmn0189 235plusmn0337 217plusmn0143 377plusmn0342 240plusmn0218 6055plusmn0176 12

Between normal and diseased

Plt 005 Plt001 Plt0001

Table (9) Ceftriaxone clearance (mlmin10kgbwt following repeated intramuscular injection of 20 mg ceftriaxone kgbwt

twice in normal and experimentally Salmonella typhimurim infected goats (n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1048plusmn121 0557plusmn684 895plusmn113 0547plusmn560 238plusmn0222 103plusmn 480 0668plusmn0157 0173plusmn216 -------- ----------- Before

156plusmn0251 43204plusmn3322 0936plusmn0162 43211plusmn3334 0473plusmn0037 43469plusmn43964 0300plusmn0028 43341plusmn080 0190plusmn0137 43400plusmn43642 050

166plusmn0079 43323plusmn3311 157plusmn0178 43419plusmn3301 137plusmn0115 43311plusmn33022 0883plusmn0054 43341plusmn 133 0616plusmn0153 43120plusmn3301 1

254plusmn0272 43361plusmn3391 222plusmn0093 4331plusmn3390 243plusmn0180 43209plusmn3309 183plusmn0149 43310plusmn2340 128plusmn0153 43312plusmn3390 2

181plusmn0136 43339plusmn3316 161plusmn0129 433plusmn3329 144plusmn0100 43412plusmn3349 0821plusmn0072 0063plusmn0977 0654plusmn0065 43400plusmn4306 4

160plusmn0177 43393plusmn336 152plusmn0200 43416plusmn331 135plusmn0118 4332plusmn3322 0897plusmn0052 43304plusmn3330 0212plusmn0022 43460plusmn43112 6

153plusmn0049 43291plusmn234 163plusmn0242 43346plusmn3300 0891plusmn0272 43306plusmn3310 108plusmn0071 43416plusmn04310 0229plusmn0046 43490plusmn43916 8

340plusmn0522 43214plusmn2341 249plusmn0150 43112plusmn3393 186plusmn0159 43320plusmn336 0773plusmn0094 43390plusmn 134 0264plusmn0043 43400plusmn 54369 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Table (10) Ceftriaxone clearancecreatinine clearance following repeated ntramuscular injection of 20 mg

ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats

(n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

0934plusmn0083 0305plusmn0013 183plusmn0116 0864plusmn0098 0358plusmn0018 0279plusmn0047 0099plusmn0020 0127plusmn0001 ------- ----------- Before

220plusmn0115 0819plusmn0044 131plusmn00414 0458plusmn0029 0876plusmn0063 126plusmn0068 0361plusmn0011 0813plusmn0031 0018plusmn0003 108plusmn0062 050

164plusmn0078 0818plusmn0029 118plusmn0068 0546plusmn0027 0858plusmn0052 0407plusmn0041 0331plusmn0009 0287plusmn0025 0324plusmn0011 0909plusmn0187 1

161plusmn0044 0488plusmn0005 232plusmn128 0329plusmn0027 169plusmn0464 0686plusmn0050 0409plusmn0020 0220plusmn0029 0512plusmn0077 266plusmn177 2

0933plusmn0024 0394plusmn0005 0948plusmn0062 0296plusmn0007 0381plusmn0027 0160plusmn0008 0235plusmn0014 0083plusmn0006 0528plusmn0028 0362plusmn0041 4

0726plusmn0018 0411plusmn0028 0639plusmn0066 0204plusmn0006 0446plusmn0034 0286plusmn0008 0238plusmn0019 0214plusmn0006 020plusmn0013 0382plusmn0028 6

0609plusmn0072 0425plusmn0036 0508plusmn0052 0192plusmn0009 0524plusmn0146 174plusmn0083 0477plusmn0015 0213plusmn00018 0109plusmn0185 0222plusmn0006 8

108plusmn0128 0496plusmn0012 0942plusmn0004 0265plusmn0030 0891plusmn0056 0706plusmn0103 0351plusmn0022 0354plusmn0018 0111plusmn0021 0098plusmn0018 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

DISCUSSION

In the present investigation intravenous injection of 20 mg ceftriaxonekgbwt in normal goats the drug showed high serum level

(92plusmn 0408 μgml) at 5 minutes post-injection then its concentration was decreased gradually till reached its minimum level (18

plusmn0816μgml) at 8hours post-injection

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In the present investigation the intravenous injection of 20 mg ceftriaxonekgbwt In normal

goats showed that the drug disposition best fitted a two-compartments- open model a

compartment of plasma and rapid equilibrating tissues and a deeper slower compartment

The obtained result is consistent with those reported for ceftriaxone in lactating goats[9]

lactating ewe[25]

domestic cat[15]

calves[26]

and patanwadi sheep[8]

Also this phenomenon is

in agreement with those reported for other cephalosporines as ceftazidime in a rabbit[27]

cefepime in dog and neonatal foals[28]

ewes[29]

ceftriaxone in goats[9]

cefipime in calves[30]

ceftiofur in cross-bred friesian cattle[31]

cefipime in calves[32]

ceftiofur in cows[33]

cefpirome

in cross-bred calves[3]

cefazidime in goats[35]

and cefquinome in sheep and goats[36]

cefipime

in chickens[37]

Ceftriaxone was distributed after intravenous injection with a distribution phase (α) equal to

656 per hour with a short distribution half ndash life [t05 (α)] equal to 0104 hour The shorter

distribution half-life of ceftriaxone in goats suggested the rapid distribution of the drug in

body tissue and fluid and that nearly similar to that recorded for ceftriaxone in lactating

goats(012 hour)[9]

for ceftriaxone in lactating ewes (0152 hour)[2]

and for ceftriaxone in

calves( 013hour)[26]

The rapid distribution of ceftriaxone in goats is supported by high rate constant of transfer of

the drug from central to peripheral compartment [K12 = 353 h-1

] as compared to the rate

constant of transfer of the drug from peripheral to central compartment [K21= 295 h-1

] This

value is nearly similar to those reported for cefotaxime in goats (K21=327 h-1

)[38]

On contrast

this value was higher than those recorded for ceftriaxone in lactating goats (K21=143 h-1

)[9]

in

lactating ewes (K21=125 h-1

)[25]

and in domestic cats (K21=154 h-1

)[15]

The apparent volume of distribution of ceftriaxone was (0355plusmn0004LKg) this value is

nearly similar to that recorded for cefaronide in sheep(039 LKg)[7]

cefotaxime in dog (048

lkg)[39]

in goat (051 lkg)

[40] for caphalexin in buffalo calves (041 Lkg)

[41] for cefipime in

ewes and calves (032 lkg) (043Lkg)[29]

and[30]

respectively For ceftriaxone in domestic

cats (057Lkg)[15]

in camel (032Lkg)[42]

On the other hand this result is differ than that

reported for cefotaxime in buffalo calves (117Lkg)[43]

High value of the volume of

distribution suggested extensive penetration power Drug with volume of distribution greater

than one literkilogram indicated wide distribution or extensive tissue binding or both[44]

The

apparent volume of distribution in the present study indicated moderate tissue penetrating

power This result agreed with[15]

for ceftriaxone in domestic cats

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

Ceftriaxone is eliminated in the current study following a single intravenous injection with

elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the

data recorded for ceftizoxime in goats (624hours)[45]

On contrast this value was longer than

that reported for ceftriaxone in lactating ewe (175hours)[25]

for cefaronide in sheep (17

hours)[7]

For cephalexin in buffulo calves (216hours)[41]

for ceftriaxone in healthy horse

(162hours)[46]

also this value is longer than that recorded for ceftriaxone in lactating goats

(144hours)[9]

for cefipime in goats (186hours)[47]

The rate of total body clearance of ceftriaxone following a single intravenous injection is

0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]

On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating

goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)

(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]

respectively

The variation in total body clearance might be attributed to specific interspecies variation

handling of the drug method used healthy status of the animal[48]

The difference between values calculated for pharmacokinetic parameters may be attributed

to animal species the drug formulation employed the age the size or sex o l lf the animal

or even inter individual variation and also due to method of analysis of the drug[49]

Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the

drug reached its peak serum concentrations after one hour of injection with value

of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12

hours post-injection The reported peak serum concentrations neerly similar to that reported

for cephalexin in buffulo calves (457 microgml)[41]

These results is differed than those reported

for ceftriaxone in cross breed calves (188 microgml at 30 min[16]

in Kangro breed of goats

(Capra Hircus) (2640 microgml at 20 min[10][50]

found after intramuscular administration of

ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher

than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]

The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time

(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats

(4932 microgml[47]

The reported maximum serum concentration (Cmax) is higher than that

reported for ceftriaxone in lactating goats(236 microgml)[9]

in lactating ewes (1722 microgml[25]

in

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

goats (2151 microgml)[11]

for cefquinome in camels (123 microgml)[51]

for ceftriaxone in calves

(1534 microgml)[26]

in patanwadi sheep (1553 microgml)[8]

for cefpirome in cattle (101 microgml)[52]

And for ceftiofur in chickens (2594 μgml)[37]

On the other hand the result was lower than

that reported by[6]

who observed the maximum serum concentration (Cmax) of ceftriaxone in

human after ntramuscular administration was (805 microgml) also it was lower than that

reported for ceftriaxone in dog (11510 microgml)[53]

in domestic cats (5440 microgml)[15]

and for

ceftazoxime in goats (8878 microgml)[45]

The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating

ewes by[25]

On contrast it is longer than those reported for ceftriaxone in dogs

(129hours)[53]

for ceftriaxone in lactating goats (07hours)[9]

also the result was longer than

that reported for ceftriaxone in domestic cats (033hours)[15]

in buffulo calves (05 hours)[13]

and for cefpirome in cattle (075hours)[52]

The reported [tmax] is shorter than those reported

for cefquinome in camels (425hours)[51]

in sheep and goats (261 and 262 hours)[36]

and for

ceftiofur in chickens (251 hours)[37]

The elimination half life [t05(β)]

following a single intramuscular administration was 1804 hours This value is nearly agreed

with that recorded for cefquinomein camels (1024hours)[52]

On contrast this result is longer

than that reported for cephalexin in buffalo calves (243hours)[41]

for ceftriaxone in lactating

ewes (177hours)[25]

in buffalo calves (438hours)[13]

in goats (203 hours)[11]

and for

cefipime in goats (165 hours)[47]

The rate of total body clearance of ceftriaxone following a single intramuscular injection is

0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves

(401Lkgh)[13]

in goats (304 Lkgh)[11]

and in sheep (222 Lkgh)[8]

Bioavailability is the fraction of the drug administered by non vascular rout that gains

accesses to the systemic circulation The obtained result revealed that the calculated systemic

bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves

(61)[54]

It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]

On the other

hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]

for ceftriaxone in goats (59)[11]

in calves (47)[55]

On contrast this value is lower than

those reported for cefotaxime in two cats 982 and 93)[57]

for cephradine in goats

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

(739)[58]

for ceftazidime in a rabbit (966)[27]

for ceftriaxone in lactating goats (85)[9]

in lactating ewes (836)[25]

in domestic cats 8572[15]

for cefipime in goats 8645[47]

for ceftriaxone in buffulo calves 702[13]

and for ceftiofur in chickens 8890[37]

Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium

infected goats twics dialy for five days revealed that the drug could be detected in a

therapeutic level for 12hours following repeated intramuscular administrations and exceeded

the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]

The relative higher serum concentrations of ceftriaxone after the last dose compared to the

first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12

hours intervals for five consecutive days These observations agreed with data reported by[36]

on comparing the data of serum levels of repeated intramuscular injections with first

intramuscular injection it was revealed that repeated intramuscular injections of cefquinome

have cumulative effect in both species sheep and goats

The obtained result is inconsistent with that reported by[56]

who found thatwhen cefotaxime

was administered repetitively in patients the ratio of maximal serum levels after the last dose

to those after the first dose demonstrated minimal accumulation of intact drug and by[60]

who

found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in

buffalo calves

The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium

infected goats are significantly lower than those in normal goats following repeated

intramuscular injection These lower blood concentrations in Salmonella typhimurium

infected goats might be attributed to the higher penetrating power of ceftriaxone to the

diseased tissues[48]

This phenomenon is similar to data recorded by[61]

who suggested that

Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of

ceftriaxone These alterations might be due to fever and inflammation induced by

infections[59]

proved that the serum concentrations of cephradine following intramuscular

administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after

each intramuscular dose with a lower significant values recorded in Escherichia-coli infected

goats than in normal goatsAlso similer to that reported by[62]

who observed that the

maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

in comparison to normal sheepOn contrast[43]

reported that peak plasma level of cefotaxime

in febrile buffalo calves was higher than healthy buffalo calves

In this study the total body clearance (CLtot) in normal goats are significantly lower than in

Salmonella typhimurium infected goats This result supported by[61]

and[63]

fever and

inflammation are cardinal features in bacterial infection which may in turn caused an

increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all

these could lead to increased in the rate at which the drug was delivered to both organs which

were important sites of drug excretion This might somewhat explain the increase in the total

body clearance in infected goats This result is differ than that reported by[64]

who observed

that the clearance of ceftriaxone was significantly reduced in infected mice than in non

infected animals

The highest concentrations of ceftriaxone in milk are recorded 4 hours after each

intramuscular injection with a significant lower value in Salmonella typhimurium infected

goats than in normal goats This might be attributed to accumulation of drug in the inflammed

tissues[48]

This result is similar to those reported by[6559]

who found that milk concentrations

of gentamicin and cephradine were significantly lower in infected goats and cattle than in

normal ones respectively

The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the

non-ionic passive diffusion principle[66]

reported that most drug cross-lipid membranes by

passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly

influenced by the physicochemical properties of the drug[6768]

Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum

ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the

physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]

Milk

contains substantially more lipid and less protein than serum and is slightly more acidic

Therefore drugs which tend to concentrated in milk are weak bases with low serum protein

binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide

and aminothiazole also possesses an hydroxytriazinone group as new and additional

ionization center[70]

these compounds are sufficiently lipid- soluble to be able to penetrate

tissues

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The dose of ceftriaxone used in the present study induced therapeutically concentrations in

milk These concentrations suggested that ceftriaxone would be efficacious in treatment of

mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily

for 3-5 days

The study showed that the urine concentrations of ceftriaxone are greater than the concurrent

serum concentrations following intramuscular injection This observation is similar to those

reported in cows after cephapirin administrations[71]

In the present study urine concentrations of ceftriaxone increased with the repetition of

dosing This observation supported by[72]

after repeated intramuscular administrations of

ceftriaxone in healthy volunteeres

The mean peak urine concentrations of ceftriaxone were reached 2 hours after each

intramuscular injection The lower urine ceftriaxone concentrations in Salmonella

typhimurium infected goats than in normal goats might be attributed to the accumulation of

the drug in the inflamed tissues[48]

The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower

ratio in Salmonella typhimurium infected goats than in normal goats at different time of

sampling This indicates that glomerular filteration seemed to be the main pathway of

ceftriaxone elimination This observation supported by[59]

who found that the ratio between

cephradine clearance from blood of goats to creatinine clearance showed a marked decrease

in Escherichia-coli infected goats than in normal goats This indicated that glomerular

filteration seemed to be the main pathway of cephradine elimination with a limited rate of

tubular reabsorption

CONCLUSION

The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value

referred a better absorption of ceftriaxone from its site of intramuscular administration The

high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular

administrations suggested that ceftriaxone could be used for treatment of mastitis caused by

Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats

The high concentrations of ceftriaxone in urine after repeated intramuscular administrations

suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections

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caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in

goats

REFERANCES

1 Neu HC Merpol NJ and Fukp (1981) Antibacterial activity of ceftriaxone

abetalactamase stable cephalosporines Antimicrobial agents and chemotherapy 19

414-423

2 Richard DM Heel RC Brogden RN Speight TM Avery GS (1984) Ceftriaxone a

review of its antibacterial activity pharmacological properties and therapeutic uses

Drugs 27 469-527

3 Brogden RN and Ward A (1988) Ceftriaxone a reappraisal of its antibacterial activity

and pharmacokinetic properties and an update on its therapeutic use with particular

reference to once-daily administration Drugs 35 604-645

4 Waxman DJ and Strominger JL (1983) Penicillin-binding proteins and the

mechanism of action of beta-lactam antibiotics Annu Rev Biochem 52(1) 825-869

5 Christ W (1991) properties of cephalosporines Infestion 19 244-252

6 Goonetilleke AK Dev D Aziz I Hughes C Smith MJ Basran GS (1996) A

comparative analysis of pharmacokinetics of ceftriaxone in serum and pleural fluid in

humans a study of once daily administration by intramuscular intravenous routes J

Antimicrob Chemother Dec 38(6) 969-76

7 Guerrini VH Filippich LJ Cao G R English PB Bourne DW (1985)

Pharmacokinetics of cefaronide ceftriaxone and cefperazone in sheep J Vet Pharmacol

Ther 8(2) 120-7

8 Swati Tiwari S Patel UD Bhavsar SK and Thaker AM (2010) Pharmacokinetics

and Bioavailability of Ceftriaxone in Patanwadi Sheep Online veterinary journal 5(2)

9 Ismail MM (2005) Pharmacokinetics urinary and mammary excretion of ceftriaxone in

lactating goats J Vet Med A Physiol Pathol Clin Med Sep 52(7) 354-8

10 Rajinder R prawez S Srivastiva AS (2005) Pharmacokinetics and dosage regimen of

ceftriaxone following its single ntramuscular adminsteration in kagani breed of goats

(Capra Hircus) Journal of reaserch 4(2) 91-93

11 Tiwari S Swati Bhavsar SK Patel UD and Thaker AM (2009) Disposition of

Ceftriaxone in Goats (Capra hircus) Online veterinary journal 4(2)

12 Dardi MS Sharma SK and Srivastava AK (2004) Pharmacokinetics and Dosage

regimen of ceftriaxone in buffalo calves Vet Res Commun 28 331-338

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INTRODUCTION

Ceftriaxone is a third-generation semi-synthetic bactericidal cephalosporin antibiotic

resistant to various types of bacterial β-lactamases It has excellent activity against gram

negative bacteria as well as a wide range of gram-positive and some anaerobic bacteria

including enterobacteriaceae Streptococcus pneumoniae Haemophilus inflfl uenzae

Pseudomonas aeruginosa and other non-enterococcal streptococci[123]

Like other

cephalosporin ceftriaxone bind to the penicillin-binding proteins (PBP) by covalent bond and

inactivate transpeptidase enzymes thereby inhibiting the peptidoglycan synthesis leading to

inhibition of the cell wall synthesis[4]

It has rapid absorption and wide distribution in tissues

as well as body fluids after parenteral administration in animals[5]

The drug thus seems to be

useful in the treatment of a variety of bacterial infections including meningitis septicemia

pyoderma colibacillosis surgical prophylaxis and urinary tract respiratory tract wound soft

tissue and joint infections[2]

Clinical pharmacology of ceftriaxone was investigated in human[6]

sheep[78]

goats[91011]

buffulo calves[1213]

calves[14]

domestic cats[15]

cross bred cow calves[16]

Little literature was

found concerning the pharmacokinetics of ceftriaxone in goats Thus the aim of present

work was undertaken to study the pharmacokinetic parameters of ceftriaxone after

intravenous and intramuscular injection in normal and experimentally Salmonella

typhimurium infected goats also the bioavailability of ceftriaxone was calculated after a

single intramuscular injection in normal goats

MATERIAL AND METHODS

Drug

Ceftriaxone is a member of third generation cephalosporins ceftriaxone sodium was used in

this study under the trade name (Cefaxonereg) It is available as glass vial containing 1000 mg

ceftriaxone it was produced by Pharco company Egypt

Experimental animals

Four clinically normal lactating baladi four experimentally infected goats and lactating goats

were used for each drug in this investigation The body weight and age of the tested goats

ranged from 20-26 kg and from 2 to 3 years old (for normal goats) and from 22 ndash 29 kg and

from 25 to 35 years old for experimentally infected goats They were housed in hygienic

stable fed on barseem drawa and concentrate Water was provided ad-libitum

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Grouping of goats

Group (1)

It included 4 normal post-partum lactating goats Each goat was injected intravenously into

the left jugular vein ceftriaxone These goats were left for 15 days after the intravenous

injection to insure complete excretion of ceftriaxone from bodies of goats Then each goat

was injected intramuscularly into the gluteus medius muscle with the same dose of

ceftriaxone The aim of intramuscular injection to calculate the bioavailability of ceftriaxone

in normal goats

Group (2)

It included 4 normal post-partum lactating goats Each goat was injected intramuscularly into

the gluteus medius muscle with 20 mgkg bwt ceftriaxone for five consecutive days

Group (3)

It included 4 experimentally infected post-partum lactating goats with twenty four hours

peptone water culture of enterpathogen Salmonella typhimurium which were cultured on

nutrient agar plates for 24 hours then suspension of culture were collected by sterile saline

By opacity tube the required concentration of 2Χ109 micro-organismsml was obtained Each

of the four goats received orally a 10 ml suspension containing 2x109

organismml The

clinical symptoms of bacteraemia as fever and diarrhea appeared after 48-72 hours of

injection with Salmonella typhimurium suspension[17]

Each goat was injected

intramuscularly into the gluteus medius muscle with ceftriaxone per kilogram body weight

48 hours after experimental infection with samlonella Typhmurium for five consecutive days

Collection of samples

Blood samples

Blood samples were collected from right jugular vein following a single intravenous injection

of ceftriaxone in normal goats blood samples were collected after 5 min 10 min15 min 30

min 1 2 4 8 and 12 hours of administration Blood samples following the second third

fourth and fifth intramuscular doses were collected before and 10 min 15 min 050 1 2 4 8

and 12 hours post injection Blood samples taken from goats were allowed to clot and the

serum separated by centrifugation collected and divided in to two parts the first part was

used for assay of ceftriaxone and the second part was used for creatinine assay All serum

samples were stored at ndash 20degC until assay for ceftriaxone and creatinine

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Urine samples

The urine sample was taken by using rubber balloon catheter (Folatex No 4158512) The

goats were catheterized and bladder was evacuated before each experiment Following

injection of ceftriaxone (single intravenous single intramuscular and repeated intramuscular

administration) in goats (normal and experimentally infected) urine samples were taken after

025 050 1 2 4 8 12 24 and 48 hours of administrations Urine sample which was taken

at 025 h was discarded Urine samples from goats of group (1) group (2) group (3) were

collected and divided into two parts the first part was used for assay of ceftriaxone and the

second part was used for creatinine assay All urine samples were stored at - 20degC until assay

for ceftriaxone After the end of each experiment the urinary bladder was irrigated with 15

milliliters potassium permanganate solution 1 5000 as antiseptic agent

Milk samples

The udder was completely evacuated before drug administration and milk samples were

collected by hand stripping from both teats Following injection of ceftriaxone (single

intravenous single intramuscular and repeated intramuscular administration) in goats (normal

and experimentally infected) milk samples were taken after 050 1 2 4 8 12 24 and 48

hours of administrations Milk sample which was taken at 025 h was discarded The udder of

each goat in all groups was completely evacuated before drug administration and after each

milk samples Milk samples from goats of all groups were allowed to clot (by mixing equal

volumes of milk and 25 trichloroacetic acid) and centrifuged The skim milk was collected

and stored at ndash 20degC until assay for ceftriaxone

Analytical Procedure

Assay of ceftriaxone

Ceftriaxone was assayed in goats serum distalled water and goats milk by microbiological

method using agar well diffusion method by using of Escherichia coli ATCC (American

type culture collection 25922) as tested microorganism which was obtained from

Microbiological Department Animal Health Institute Doky Giza Egypt)[18]

Concentrations of ceftriaxone in biological fluids were determined by modification of the

agar ndash plate diffusion method[19]

using Escherichia coli ATCC25922 as assay organism and

Muller Hinton agar media

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Assay of samples

According to[20]

three plates were used for each sample Six pores were made three of them

were filled with reference concentration while the other three pores were filled with the

serum milk or urine samples in triplicate manner The plates were incubated at 37degC for 18

hours then the diameter of inhibitory zones were measured The diameter of inhibitory zones

of samples were corrected by using the zone diameter of the reference concentration in the

same manner as previously discussed either by addition or subtraction From the standard

curve the concentrations corresponding to the corrected values of the inhibitory zones were

obtained

Drug clearance

Clearance of the tested drug from the blood of goats was estimated according to the following

equation

Drug clearance10 kg b wt =

Drug concentration in urine (microgml) X rate of diuresis (mlmin) Body weight (Kg)

_________________________________________________________________

Drug concentration in serum (microgml) X 10

Assay of creatinine in serum and urine

Creatinine was assayed by[21]

and performed by kit manufactured by Diamond diagnostics

company

Creatinine clearance

The creatinine clearance (mlmin10 kgbwt) for goats was calculated by the following

equation

Creatinine clearance 10 kgbwt =

Creatinine concentration in urine (mgL) X rate of diuresis (mlmin) Body weight (Kg)

______________________________________________________________________

Creatinine concentration in serum (mgL) X 10

Pharmacokinetic analysis

The pharmacokinetic parameters were calculated by using Winonlin version 12 and other

parameters according to[2223]

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Statistical Analysis

The data were calculated as mean plusmn standard error All statistical analysis were carried out

according to[24]

using the scientific calculator CASIO fx 120

RESULTS

Following a single intravenous injection of 20 mg ceftriaxonekg bwt in normal goats

ceftriaxone could be detected therapeutically for 8 hours post intravenous injection The

serum concentration ndash time curve of ceftriaxone following intravenous injection showed that

the drug obeyed a two compartments open model (Figure 1) The disposition kinetics of

ceftriaxone following a single intravenous intramuscular injection were recorded in table (1)

Intramuscular injection of 20 mg ceftriaxone per kilogram body weight twice daily for five

consecutive days in normal and Salmonella typhimurium infected goats revealed a lower

significant serum ceftriaxone concentration after the first third fifth seventh ninth doses in

Salmonella typhimurium infected goats compared with normal goats The pharmacokinetic

parameters of ceftriaxone after repeated intramuscular injection in normal were compared to

those in Salmonella typhimurium infected goats (Table 2) and (Figure 2 amp 3)

The highest concentrations of ceftriaxone in milk were recorded 4 hours after each

intramuscular dose (Table 3) with a significant lower value in Salmonella typhimurium

infected goats compared with normal goats The calculated milkserum concentrations ratios

of ceftriaxone after repeated intramuscular injection (Table 4)

The amount of urine (mlmin) voided after repeated intramuscular injection of 20 mgkg bwt

Twice daily of ceftriaxone for five consecutive days in normal and experimentally

Salmonella typhimurium infected goats were recorded in table (5) The mean peak urine

concentrations of ceftriaxone (Table 6) were reached 2 hours after each intramuscular dose

with a lower significant concentration in Salmonella typhimurium infected goats compared

with normal goats Urineserum concentration ratios of ceftriaxone after repeated

intramuscular injection in normal and experimentally Salmonella typhimurium infected goats

were calculated and illustrated in table (7) Creatinine clearance (mlmin10 kg bwt)

expressing glomerular filtration rate from blood of goats was shown in table (8) The rate of

ceftriaxone clearance (mlmin10 kg bwt) from blood of goats was shown in table (9) The

ratio between ceftriaxone clearance and creatinine clearance was calculated and illustrated in

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

table (10) The data revealed a significant lower ratio in Salmonella typhimurium infected

goats compared with normal goats after the third fifth seventh ninth doses

Table (1) Pharmacokinetics parameters of ceftriaxone (μgml) following a single

intravenous and intramuscuer injection of 20 mgkg bwt in normal goats (n=4)

Intramusculer_

(XplusmnS E)

Intravenous_

(XplusmnS E) Unit Parameters

-------- 1213 plusmn321321 microgml Cdeg

4360plusmn12343 61390 plusmn330 microgml A

43440plusmn43660 636 plusmn43316 h-1

α

43433plusmn3340 43340 plusmn43442 H (α) 43 T

43420plusmn43233 4333plusmn131 h-1

K12

43446plusmn43400 43409plusmn231 h-1

K21

-------- 43440plusmn431 lkg Vdss

4321plusmn6340 43636plusmn1303 microgml B

434446plusmn43419 43443plusmn43136 h-1

β

43141plusmn39340 43411plusmn331 H t05(β))

4344plusmn43401 434440plusmn43409 lkgh Cl tot

-------- 1136plusmn2111300 microgmlh AUMC

-------- 43303 plusmn0314 H MRT

9300plusmn2439 30plusmn034330 microgmlh AUC

3392plusmn63329 -------- F

43436plusmn4361 -------- h-1

K01

43420plusmn3346 -------- h-1

T05(k01)

4342plusmn330 -------- H Tmax(calc))

43021plusmn04343 -------- μgml Cmax(calc)

Cdeg Drug concentration in the serum at zero time immediately after a single intravenous

injection (μgml) A amp B Zero time plasma drug concentration intercepts of biphasic

intravenous disposition curve The coefficient B is based on the terminal exponential phase

(μgml) α amp β Hybrid rate constant of biphasic intravenous disposition curve values of α

and β are related to the slopes of distribution and elimination phase respectively of

biexponential drug disposition curve (h-1

) T05 (α) Distribution half ndash life (h) t05 (β)

Elimination half ndash life (h) K12 First ndash order transfer rate constant for drug distribution from

Central to peripheral compartment (h-1

) K21 First order transfer rate constant for drug

distribution from Peripheral to central compartment (h-1

) Vdss The apparent volume of

distribution which was calculated by steady ndash state method (mlkg) AUMC Area under

moment curve MRT Mean residence time AUC Total area under the serum drug

concentration versus time curve from t = 0 to t = α after administration of a single dose F

Bioavailability Cmax maximum drug concentration Tmax time of maximum observed

concentration in blood

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Figure (1) Arthimatic plot of Serum concentrations of ceftriaxone (μgml) in normal

goats following a single intramuscular injection )diamsdiams( previously given the same doseby

a single intravenous injection () of 20 mg ceftriaxonekgbwt (n=4)

Figure (2) Semilogarthmic graph depicting the time course of ceftriaxone in serum of

normal goats following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt

twice dialy for five consecutive days (n=4)

Figure (3) Semilogarthmic graph depicting the time course of ceftriaxone in serum of

experimentally Salmonella typhimurim infected goats following repeated ntramuscular

injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4) 3

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Table (2) Pharmacokinetic parameters of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected

goats following repeated ntramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)

Dose

Unit

عىهParameters

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1269plusmn0073 7409plusmn121 1352plusmn0132 6373plusmn147 1410plusmn0243 5923plusmn126 1461plusmn0214 5430plusmn125 1424plusmn0172 7635plusmn176 gmlmicro A

0651plusmn0049 plusmn000843116 0720plusmn0008 plusmn00413300 0823plusmn0006 plusmn00263322 0848plusmn0025 plusmn00233323 0786plusmn0028 133plusmn0033 h-1 Α

106plusmn0008 330plusmn0015 0962plusmn0011 0392plusmn0007 0841plusmn0007 0567plusmn012 0818plusmn0024 0569plusmn0012 0885plusmn0030 plusmn00124322 H T05(α)

248plusmn0019 168plusmn0047 203plusmn0075 181plusmn0033 267plusmn0039 120plusmn0028 248plusmn0060 122plusmn0026 222plusmn0100 136plusmn0027 h-1 Kab

0278plusmn0002 0412plusmn0009 0342plusmn0012 0383plusmn0008 0252plusmn0009 0567plusmn0011 0279plusmn0005 00569plusmn0011 0314plusmn0014 0 510plusmn0012 H T05(ab)

0627plusmn0008 0378plusmn0007 0430plusmn0008 0402plusmn0008 0113plusmn00027 0424plusmn0009 0117plusmn0004 0394plusmn0008 0116plusmn0003 0239plusmn0005 h-1 K12

121plusmn0013 0962plusmn0022 141plusmn0021 130plusmn0023 0666plusmn0019 0651plusmn0013 0683plusmn0020 0660plusmn0013 0761plusmn0039 0998plusmn0023 h-1 K21

115plusmn0035 129plusmn0026 104plusmn0047 112plusmn0024 106plusmn0037 122plusmn0025 110plusmn0077 119plusmn0023 0910plusmn0032 123plusmn0023 H Tmax

4182plusmn0628 6108plusmn140 3440plusmn0363 5135plusmn0860 3117plusmn0965 4774plusmn0854 2713plusmn0781 4243plusmn0 870 2479plusmn0547 4065plusmn0825 gmlmicro Cmax

4944plusmn0820 7195plusmn142 4199plusmn0702 6511plusmn130 3190plusmn0688 5117plusmn113 3185plusmn0909 4709plusmn0990 3256plusmn0918 6329plusmn139 gmlmicro B

0164plusmn0003 0189plusmn00043 0181plusmn0002 0178plusmn0004 0181plusmn00035 0167plusmn0004 0214plusmn0009 0195plusmn0005 0249plusmn0918 0272plusmn0006 h-1 β

423plusmn0079 367plusmn0086 381plusmn0047 388plusmn0089 382plusmn0074 415plusmn0081 325plusmn0139 355plusmn0075 277plusmn0056 255plusmn0050 H T05β

0879plusmn0015 0429plusmn0009 109plusmn0004 0426plusmn0009 133plusmn0022 0503plusmn0011 154plusmn0064 0675plusmn0013 171plusmn0060 0693plusmn0014 Lkgh Cltot

28358plusmn215 40775plusmn808 21784plusmn0888 34259plusmn720 17860plusmn155 30705plusmn601 15281plusmn239 24135plusmn555 12175plusmn144 20292plusmn487 gmlhmicro AUC

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (3) Milk concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats

following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)

Dose Time of

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

197plusmn0205 200plusmn0408 125plusmn0104 155plusmn0132 0887plusmn0013 0885plusmn014 0500plusmn0040 074plusmn0012 ------------ ------ Before

200plusmn0408 22plusmn0108 197plusmn0205 200plusmn0408 155plusmn0132 197plusmn0205 100plusmn000 155plusmn0132 ----------- -------- 050

526plusmn0166 700plusmn0408 300plusmn0408 64plusmn0163 25plusmn0204 600plusmn0408 155plusmn0132 582plusmn0118 100plusmn000 520plusmn0166 1

640plusmn0163 900plusmn0408 582plusmn0118 792plusmn0114 582plusmn0118 755plusmn0221 275plusmn0061 700plusmn0408 200plusmn0408 691plusmn0176 2

900plusmn0408 1512plusmn0125 640plusmn0163 1475plusmn0322 640plusmn0163 1400plusmn0408 600plusmn0408 1352plusmn0205 526plusmn166 1225plusmn0595 4

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

350plusmn0353 400plusmn0408 300plusmn0408 392plusmn0125 300plusmn0408 35plusmn0353 275plusmn006 300plusmn0408 155plusmn0132 275plusmn0061 6

300 plusmn0408 35plusmn0353 125plusmn0104 200plusmn0408 125plusmn0104 155plusmn01 0825plusmn0062 100plusmn000 0500plusmn0040 0887plusmn0013 8

200plusmn0408 22plusmn0108 100plusmn000 155plusmn0132 100plusmn000 125plusmn0104 0730plusmn002 0825plusmn0078 0422plusmn000 073plusmn0020 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (4) Milkserum concentrations ratios of ceftriaxone in normal and experimentally Salmonella typhimurim infected

goats following repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice daily for five consecutive days (n=4)

Dose Time of

a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

0400plusmn0049 025plusmn0063 0307plusmn0026 021plusmn0019 0365plusmn00064 016plusmn0026 0232plusmn0016 0205plusmn0002 -------- helliphelliphelliphellip Before

0057plusmn0125 0042plusmn00025 0062plusmn00062 0042plusmn0010 0575plusmn00062 0055plusmn0006 0067plusmn0016 0049plusmn0005 --------- -------- 050

0127plusmn00062 0115plusmn00064 008plusmn0012 0117plusmn0004 0088plusmn00054 0122plusmn0008 008plusmn0017 0126plusmn0028 0039plusmn0005 0122plusmn0004 1

018plusmn0008 0185plusmn0010 021plusmn0004 017plusmn0004 0182plusmn0054 0179plusmn0006 0112plusmn00025 0193plusmn0012 0097plusmn0020 019plusmn0004 2

0357plusmn0020 0425plusmn0005 033plusmn0021 045plusmn0009 0285plusmn0082 0494plusmn0015 0395plusmn0016 0572plusmn001 0415plusmn0017 054plusmn0027 4

018plusmn0015 016plusmn0016 0207plusmn0022 0175plusmn0006 0257plusmn0037 0180plusmn0017 0272plusmn0015 0201plusmn003 0196plusmn0016 0222plusmn0002 6

0212plusmn0033 0212plusmn0020 0200plusmn0044 0122plusmn0024 0152plusmn0011 014plusmn0022 0122plusmn00062 0102plusmn0001 0107plusmn00094 0117plusmn0002 8

0372plusmn0042 025plusmn001 0325plusmn0027 0192plusmn0014 0265plusmn00064 0185plusmn0015 0272plusmn0125 0195plusmn0012 0252plusmn0032 0275plusmn0009 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

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Table (5) The amount of urine (mlmin) voided in normal and experimentally Salmonella typhimurim infected goats following

repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)

Dose Time of a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

plusmn00372344 126plusmn0034 130plusmn0030 130plusmn0028 118plusmn0066 118plusmn0067 108plusmn0013 108plusmn0008 ----------- -------- Before

0577plusmn0069 43494057plusmn 045plusmn0060 plusmn0064309 0312plusmn002 033plusmn0012 0340plusmn0024 033plusmn0012 0287plusmn0017 0272plusmn0014 050

0712plusmn0019 0692plusmn0014 068plusmn0081 0697plusmn0006 0672plusmn0011 0675plusmn 0009 0635plusmn0032 0655plusmn0010 0719plusmn0031 0697plusmn0015 1

0837plusmn0025 0787plusmn0021 0732plusmn0011 plusmn00054300 0715plusmn0011 0715plusmn002 0722plusmn0019 0702plusmn0018 0737plusmn0027 0762plusmn0041 2

0535plusmn0095 0507plusmn0021 0447plusmn0022 0452plusmn002 0402plusmn0075 0405plusmn0011 0400plusmn0057 0397plusmn0009 0380plusmn0004 038plusmn001 4

0437plusmn00094 0432plusmn0008 0400plusmn0010 0405plusmn0002 0380plusmn0007 plusmn00044319 0372plusmn0047 037plusmn 0007 0350plusmn0005 0365plusmn0006 6

0397plusmn0028 0410plusmn0008 0380plusmn0012 0395plusmn0009 0355plusmn0086 0352plusmn0007 0340plusmn0004 0345plusmn0005 0302plusmn0004 0335plusmn0005 8

0385plusmn001 0380plusmn0010 0385plusmn00064 0380plusmn0008 0365plusmn0064 0367plusmn0004 0362plusmn0086 0372plusmn0106 0327plusmn0006 0362plusmn0016 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (6) Urine concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats

following repeated intramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)

Dose Time of a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1125plusmn150 1125plusmn15 735plusmn287 81plusmn324 183plusmn03 555plusmn798 37plusmn0811 1815plusmn43290 -------------- ------ Before

2415plusmn357 2625plusmn374 1695plusmn788 249plusmn574 10575plusmn64 2415plusmn357 5400plusmn273 2085plusmn991 102plusmn160 168plusmn547 050

26025plusmn787 2923plusmn479 22425plusmn1225 2805plusmn35 1695plusmn618 2705plusmn471 10200plusmn547 2415plusmn357 6975plusmn225 22425plusmn894 1

29295plusmn765 3012plusmn346 28575plusmn738 2964plusmn415 2355plusmn259 2923plusmn479 1635plusmn561 2645plusmn917 102plusmn547 24825plusmn616 2

23475plusmn430 2482plusmn616 23475plusmn1564 2415plusmn357 1695plusmn788 198plusmn848 8475plusmn309 1515plusmn708 60plusmn212 1185plusmn45 4

1905plusmn45 2355plusmn259 153plusmn519 1935plusmn960 114plusmn948 159plusmn173 6675plusmn309 1215plusmn45 1312plusmn0552 855plusmn193 6

153plusmn1024 1965plusmn135 1335plusmn1229 150plusmn34 735plusmn295 1365plusmn665 6181plusmn339 72plusmn244 907plusmn0951 5025plusmn143 8

135plusmn519 120plusmn346 11725plusmn1551 96plusmn874 525plusmn295 75plusmn173 153plusmn130 39plusmn212 3735plusmn0458 13125plusmn0552 12

Between normal and diseased

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Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (7) Urineserum concentrations ratios of ceftriaxone following repeated ntramuscular injection of 20 mg

ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats

(n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

229plusmn 163 1448plusmn0743 1885plusmn159 1125plusmn0484 533plusmn0260 1050plusmn358 175plusmn0380 4146plusmn116 ------- ------ Before

741plusmn0063 plusmn01553 58plusmn0242 plusmn0149390 422plusmn0206 683plusmn0106 245plusmn0092 667plusmn0306 0510plusmn0081 559plusmn0181 050

651plusmn0243 plusmn0065031 637plusmn0373 plusmn014431 565plusmn0243 plusmn0085300 360plusmn0303 plusmn0110312 279plusmn0121 534plusmn0248 1

836plusmn0150 plusmn00476322 862plusmn0180 plusmn010463 942plusmn0166 plusmn0130631 217plusmn0303 727plusmn0256 508plusmn0186 plusmn01680340 2

939plusmn0235 plusmn01580344 1006plusmn0710 plusmn00750310 999plusmn0542 plusmn02850344 565plusmn0223 641plusmn0241 48plusmn0164 plusmn014834 4

1005plusmn0418 2plusmn018813 1097plusmn0641 plusmn03979300 993plusmn0921 plusmn0252931 619plusmn0483 plusmn0362933 167plusmn0101 642plusmn0644 6

1091plusmn0649 plusmn075332339 1171plusmn0980 995plusmn0415 925plusmn0593 plusmn05593433 886plusmn0408 plusmn02510311 2055plusmn0311 plusmn02046310 8

2392plusmn129 plusmn032731396 1794plusmn0228 1222plusmn124 1418plusmn109 plusmn026733336 580plusmn0397 plusmn03951326 227plusmn0452 plusmn02740316 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (8) Creatinine clearance (mlmin10kgbwt) following repeated intramuscular injection of 20 mg ceftriaxonekgbwt

twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats (n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1115plusmn0703 2265plusmn167 481plusmn0409 672plusmn0817 669plusmn0672 1202plusmn0777 695plusmn0634 1724plusmn179 ----------- ------ Before

0703plusmn0091 147plusmn0305 0718plusmn0141 251plusmn0707 0547plusmn0055 0699plusmn0092 0802plusmn0099 103plusmn0106 295plusmn0124 0458plusmn0037 050

101plusmn0075 161plusmn0093 131plusmn0099 264plusmn0217 161plusmn0146 373plusmn0499 247plusmn0110 4755plusmn0582 214plusmn0234 103plusmn0166 1

157plusmn0198 387plusmn0340 173plusmn0501 267plusmn0217 187plusmn0563 287plusmn0499 451plusmn0223 972plusmn105 263plusmn0399 169plusmn0454 2

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

184plusmn0095 346plusmn0444 173plusmn0501 436plusmn0599 383plusmn0299 682plusmn0584 328plusmn0253 119plusmn153 123plusmn0057 292plusmn0742 4

221plusmn0242 411plusmn0661 241plusmn0186 663plusmn0584 308plusmn0234 422plusmn0314 353plusmn0393 548plusmn0901 105plusmn0057 264plusmn0294 6

261plusmn0295 476plusmn0339 319plusmn0273 753plusmn0676 106plusmn0207 0773plusmn0049 228plusmn0175 456plusmn0340 206plusmn0160 404plusmn0419 8

310plusmn0218 409plusmn0434 3264plusmn0153 669plusmn0476 209plusmn0189 235plusmn0337 217plusmn0143 377plusmn0342 240plusmn0218 6055plusmn0176 12

Between normal and diseased

Plt 005 Plt001 Plt0001

Table (9) Ceftriaxone clearance (mlmin10kgbwt following repeated intramuscular injection of 20 mg ceftriaxone kgbwt

twice in normal and experimentally Salmonella typhimurim infected goats (n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1048plusmn121 0557plusmn684 895plusmn113 0547plusmn560 238plusmn0222 103plusmn 480 0668plusmn0157 0173plusmn216 -------- ----------- Before

156plusmn0251 43204plusmn3322 0936plusmn0162 43211plusmn3334 0473plusmn0037 43469plusmn43964 0300plusmn0028 43341plusmn080 0190plusmn0137 43400plusmn43642 050

166plusmn0079 43323plusmn3311 157plusmn0178 43419plusmn3301 137plusmn0115 43311plusmn33022 0883plusmn0054 43341plusmn 133 0616plusmn0153 43120plusmn3301 1

254plusmn0272 43361plusmn3391 222plusmn0093 4331plusmn3390 243plusmn0180 43209plusmn3309 183plusmn0149 43310plusmn2340 128plusmn0153 43312plusmn3390 2

181plusmn0136 43339plusmn3316 161plusmn0129 433plusmn3329 144plusmn0100 43412plusmn3349 0821plusmn0072 0063plusmn0977 0654plusmn0065 43400plusmn4306 4

160plusmn0177 43393plusmn336 152plusmn0200 43416plusmn331 135plusmn0118 4332plusmn3322 0897plusmn0052 43304plusmn3330 0212plusmn0022 43460plusmn43112 6

153plusmn0049 43291plusmn234 163plusmn0242 43346plusmn3300 0891plusmn0272 43306plusmn3310 108plusmn0071 43416plusmn04310 0229plusmn0046 43490plusmn43916 8

340plusmn0522 43214plusmn2341 249plusmn0150 43112plusmn3393 186plusmn0159 43320plusmn336 0773plusmn0094 43390plusmn 134 0264plusmn0043 43400plusmn 54369 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Table (10) Ceftriaxone clearancecreatinine clearance following repeated ntramuscular injection of 20 mg

ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats

(n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

0934plusmn0083 0305plusmn0013 183plusmn0116 0864plusmn0098 0358plusmn0018 0279plusmn0047 0099plusmn0020 0127plusmn0001 ------- ----------- Before

220plusmn0115 0819plusmn0044 131plusmn00414 0458plusmn0029 0876plusmn0063 126plusmn0068 0361plusmn0011 0813plusmn0031 0018plusmn0003 108plusmn0062 050

164plusmn0078 0818plusmn0029 118plusmn0068 0546plusmn0027 0858plusmn0052 0407plusmn0041 0331plusmn0009 0287plusmn0025 0324plusmn0011 0909plusmn0187 1

161plusmn0044 0488plusmn0005 232plusmn128 0329plusmn0027 169plusmn0464 0686plusmn0050 0409plusmn0020 0220plusmn0029 0512plusmn0077 266plusmn177 2

0933plusmn0024 0394plusmn0005 0948plusmn0062 0296plusmn0007 0381plusmn0027 0160plusmn0008 0235plusmn0014 0083plusmn0006 0528plusmn0028 0362plusmn0041 4

0726plusmn0018 0411plusmn0028 0639plusmn0066 0204plusmn0006 0446plusmn0034 0286plusmn0008 0238plusmn0019 0214plusmn0006 020plusmn0013 0382plusmn0028 6

0609plusmn0072 0425plusmn0036 0508plusmn0052 0192plusmn0009 0524plusmn0146 174plusmn0083 0477plusmn0015 0213plusmn00018 0109plusmn0185 0222plusmn0006 8

108plusmn0128 0496plusmn0012 0942plusmn0004 0265plusmn0030 0891plusmn0056 0706plusmn0103 0351plusmn0022 0354plusmn0018 0111plusmn0021 0098plusmn0018 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

DISCUSSION

In the present investigation intravenous injection of 20 mg ceftriaxonekgbwt in normal goats the drug showed high serum level

(92plusmn 0408 μgml) at 5 minutes post-injection then its concentration was decreased gradually till reached its minimum level (18

plusmn0816μgml) at 8hours post-injection

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

In the present investigation the intravenous injection of 20 mg ceftriaxonekgbwt In normal

goats showed that the drug disposition best fitted a two-compartments- open model a

compartment of plasma and rapid equilibrating tissues and a deeper slower compartment

The obtained result is consistent with those reported for ceftriaxone in lactating goats[9]

lactating ewe[25]

domestic cat[15]

calves[26]

and patanwadi sheep[8]

Also this phenomenon is

in agreement with those reported for other cephalosporines as ceftazidime in a rabbit[27]

cefepime in dog and neonatal foals[28]

ewes[29]

ceftriaxone in goats[9]

cefipime in calves[30]

ceftiofur in cross-bred friesian cattle[31]

cefipime in calves[32]

ceftiofur in cows[33]

cefpirome

in cross-bred calves[3]

cefazidime in goats[35]

and cefquinome in sheep and goats[36]

cefipime

in chickens[37]

Ceftriaxone was distributed after intravenous injection with a distribution phase (α) equal to

656 per hour with a short distribution half ndash life [t05 (α)] equal to 0104 hour The shorter

distribution half-life of ceftriaxone in goats suggested the rapid distribution of the drug in

body tissue and fluid and that nearly similar to that recorded for ceftriaxone in lactating

goats(012 hour)[9]

for ceftriaxone in lactating ewes (0152 hour)[2]

and for ceftriaxone in

calves( 013hour)[26]

The rapid distribution of ceftriaxone in goats is supported by high rate constant of transfer of

the drug from central to peripheral compartment [K12 = 353 h-1

] as compared to the rate

constant of transfer of the drug from peripheral to central compartment [K21= 295 h-1

] This

value is nearly similar to those reported for cefotaxime in goats (K21=327 h-1

)[38]

On contrast

this value was higher than those recorded for ceftriaxone in lactating goats (K21=143 h-1

)[9]

in

lactating ewes (K21=125 h-1

)[25]

and in domestic cats (K21=154 h-1

)[15]

The apparent volume of distribution of ceftriaxone was (0355plusmn0004LKg) this value is

nearly similar to that recorded for cefaronide in sheep(039 LKg)[7]

cefotaxime in dog (048

lkg)[39]

in goat (051 lkg)

[40] for caphalexin in buffalo calves (041 Lkg)

[41] for cefipime in

ewes and calves (032 lkg) (043Lkg)[29]

and[30]

respectively For ceftriaxone in domestic

cats (057Lkg)[15]

in camel (032Lkg)[42]

On the other hand this result is differ than that

reported for cefotaxime in buffalo calves (117Lkg)[43]

High value of the volume of

distribution suggested extensive penetration power Drug with volume of distribution greater

than one literkilogram indicated wide distribution or extensive tissue binding or both[44]

The

apparent volume of distribution in the present study indicated moderate tissue penetrating

power This result agreed with[15]

for ceftriaxone in domestic cats

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

Ceftriaxone is eliminated in the current study following a single intravenous injection with

elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the

data recorded for ceftizoxime in goats (624hours)[45]

On contrast this value was longer than

that reported for ceftriaxone in lactating ewe (175hours)[25]

for cefaronide in sheep (17

hours)[7]

For cephalexin in buffulo calves (216hours)[41]

for ceftriaxone in healthy horse

(162hours)[46]

also this value is longer than that recorded for ceftriaxone in lactating goats

(144hours)[9]

for cefipime in goats (186hours)[47]

The rate of total body clearance of ceftriaxone following a single intravenous injection is

0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]

On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating

goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)

(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]

respectively

The variation in total body clearance might be attributed to specific interspecies variation

handling of the drug method used healthy status of the animal[48]

The difference between values calculated for pharmacokinetic parameters may be attributed

to animal species the drug formulation employed the age the size or sex o l lf the animal

or even inter individual variation and also due to method of analysis of the drug[49]

Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the

drug reached its peak serum concentrations after one hour of injection with value

of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12

hours post-injection The reported peak serum concentrations neerly similar to that reported

for cephalexin in buffulo calves (457 microgml)[41]

These results is differed than those reported

for ceftriaxone in cross breed calves (188 microgml at 30 min[16]

in Kangro breed of goats

(Capra Hircus) (2640 microgml at 20 min[10][50]

found after intramuscular administration of

ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher

than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]

The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time

(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats

(4932 microgml[47]

The reported maximum serum concentration (Cmax) is higher than that

reported for ceftriaxone in lactating goats(236 microgml)[9]

in lactating ewes (1722 microgml[25]

in

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

goats (2151 microgml)[11]

for cefquinome in camels (123 microgml)[51]

for ceftriaxone in calves

(1534 microgml)[26]

in patanwadi sheep (1553 microgml)[8]

for cefpirome in cattle (101 microgml)[52]

And for ceftiofur in chickens (2594 μgml)[37]

On the other hand the result was lower than

that reported by[6]

who observed the maximum serum concentration (Cmax) of ceftriaxone in

human after ntramuscular administration was (805 microgml) also it was lower than that

reported for ceftriaxone in dog (11510 microgml)[53]

in domestic cats (5440 microgml)[15]

and for

ceftazoxime in goats (8878 microgml)[45]

The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating

ewes by[25]

On contrast it is longer than those reported for ceftriaxone in dogs

(129hours)[53]

for ceftriaxone in lactating goats (07hours)[9]

also the result was longer than

that reported for ceftriaxone in domestic cats (033hours)[15]

in buffulo calves (05 hours)[13]

and for cefpirome in cattle (075hours)[52]

The reported [tmax] is shorter than those reported

for cefquinome in camels (425hours)[51]

in sheep and goats (261 and 262 hours)[36]

and for

ceftiofur in chickens (251 hours)[37]

The elimination half life [t05(β)]

following a single intramuscular administration was 1804 hours This value is nearly agreed

with that recorded for cefquinomein camels (1024hours)[52]

On contrast this result is longer

than that reported for cephalexin in buffalo calves (243hours)[41]

for ceftriaxone in lactating

ewes (177hours)[25]

in buffalo calves (438hours)[13]

in goats (203 hours)[11]

and for

cefipime in goats (165 hours)[47]

The rate of total body clearance of ceftriaxone following a single intramuscular injection is

0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves

(401Lkgh)[13]

in goats (304 Lkgh)[11]

and in sheep (222 Lkgh)[8]

Bioavailability is the fraction of the drug administered by non vascular rout that gains

accesses to the systemic circulation The obtained result revealed that the calculated systemic

bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves

(61)[54]

It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]

On the other

hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]

for ceftriaxone in goats (59)[11]

in calves (47)[55]

On contrast this value is lower than

those reported for cefotaxime in two cats 982 and 93)[57]

for cephradine in goats

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

(739)[58]

for ceftazidime in a rabbit (966)[27]

for ceftriaxone in lactating goats (85)[9]

in lactating ewes (836)[25]

in domestic cats 8572[15]

for cefipime in goats 8645[47]

for ceftriaxone in buffulo calves 702[13]

and for ceftiofur in chickens 8890[37]

Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium

infected goats twics dialy for five days revealed that the drug could be detected in a

therapeutic level for 12hours following repeated intramuscular administrations and exceeded

the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]

The relative higher serum concentrations of ceftriaxone after the last dose compared to the

first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12

hours intervals for five consecutive days These observations agreed with data reported by[36]

on comparing the data of serum levels of repeated intramuscular injections with first

intramuscular injection it was revealed that repeated intramuscular injections of cefquinome

have cumulative effect in both species sheep and goats

The obtained result is inconsistent with that reported by[56]

who found thatwhen cefotaxime

was administered repetitively in patients the ratio of maximal serum levels after the last dose

to those after the first dose demonstrated minimal accumulation of intact drug and by[60]

who

found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in

buffalo calves

The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium

infected goats are significantly lower than those in normal goats following repeated

intramuscular injection These lower blood concentrations in Salmonella typhimurium

infected goats might be attributed to the higher penetrating power of ceftriaxone to the

diseased tissues[48]

This phenomenon is similar to data recorded by[61]

who suggested that

Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of

ceftriaxone These alterations might be due to fever and inflammation induced by

infections[59]

proved that the serum concentrations of cephradine following intramuscular

administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after

each intramuscular dose with a lower significant values recorded in Escherichia-coli infected

goats than in normal goatsAlso similer to that reported by[62]

who observed that the

maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

in comparison to normal sheepOn contrast[43]

reported that peak plasma level of cefotaxime

in febrile buffalo calves was higher than healthy buffalo calves

In this study the total body clearance (CLtot) in normal goats are significantly lower than in

Salmonella typhimurium infected goats This result supported by[61]

and[63]

fever and

inflammation are cardinal features in bacterial infection which may in turn caused an

increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all

these could lead to increased in the rate at which the drug was delivered to both organs which

were important sites of drug excretion This might somewhat explain the increase in the total

body clearance in infected goats This result is differ than that reported by[64]

who observed

that the clearance of ceftriaxone was significantly reduced in infected mice than in non

infected animals

The highest concentrations of ceftriaxone in milk are recorded 4 hours after each

intramuscular injection with a significant lower value in Salmonella typhimurium infected

goats than in normal goats This might be attributed to accumulation of drug in the inflammed

tissues[48]

This result is similar to those reported by[6559]

who found that milk concentrations

of gentamicin and cephradine were significantly lower in infected goats and cattle than in

normal ones respectively

The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the

non-ionic passive diffusion principle[66]

reported that most drug cross-lipid membranes by

passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly

influenced by the physicochemical properties of the drug[6768]

Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum

ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the

physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]

Milk

contains substantially more lipid and less protein than serum and is slightly more acidic

Therefore drugs which tend to concentrated in milk are weak bases with low serum protein

binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide

and aminothiazole also possesses an hydroxytriazinone group as new and additional

ionization center[70]

these compounds are sufficiently lipid- soluble to be able to penetrate

tissues

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

The dose of ceftriaxone used in the present study induced therapeutically concentrations in

milk These concentrations suggested that ceftriaxone would be efficacious in treatment of

mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily

for 3-5 days

The study showed that the urine concentrations of ceftriaxone are greater than the concurrent

serum concentrations following intramuscular injection This observation is similar to those

reported in cows after cephapirin administrations[71]

In the present study urine concentrations of ceftriaxone increased with the repetition of

dosing This observation supported by[72]

after repeated intramuscular administrations of

ceftriaxone in healthy volunteeres

The mean peak urine concentrations of ceftriaxone were reached 2 hours after each

intramuscular injection The lower urine ceftriaxone concentrations in Salmonella

typhimurium infected goats than in normal goats might be attributed to the accumulation of

the drug in the inflamed tissues[48]

The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower

ratio in Salmonella typhimurium infected goats than in normal goats at different time of

sampling This indicates that glomerular filteration seemed to be the main pathway of

ceftriaxone elimination This observation supported by[59]

who found that the ratio between

cephradine clearance from blood of goats to creatinine clearance showed a marked decrease

in Escherichia-coli infected goats than in normal goats This indicated that glomerular

filteration seemed to be the main pathway of cephradine elimination with a limited rate of

tubular reabsorption

CONCLUSION

The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value

referred a better absorption of ceftriaxone from its site of intramuscular administration The

high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular

administrations suggested that ceftriaxone could be used for treatment of mastitis caused by

Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats

The high concentrations of ceftriaxone in urine after repeated intramuscular administrations

suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in

goats

REFERANCES

1 Neu HC Merpol NJ and Fukp (1981) Antibacterial activity of ceftriaxone

abetalactamase stable cephalosporines Antimicrobial agents and chemotherapy 19

414-423

2 Richard DM Heel RC Brogden RN Speight TM Avery GS (1984) Ceftriaxone a

review of its antibacterial activity pharmacological properties and therapeutic uses

Drugs 27 469-527

3 Brogden RN and Ward A (1988) Ceftriaxone a reappraisal of its antibacterial activity

and pharmacokinetic properties and an update on its therapeutic use with particular

reference to once-daily administration Drugs 35 604-645

4 Waxman DJ and Strominger JL (1983) Penicillin-binding proteins and the

mechanism of action of beta-lactam antibiotics Annu Rev Biochem 52(1) 825-869

5 Christ W (1991) properties of cephalosporines Infestion 19 244-252

6 Goonetilleke AK Dev D Aziz I Hughes C Smith MJ Basran GS (1996) A

comparative analysis of pharmacokinetics of ceftriaxone in serum and pleural fluid in

humans a study of once daily administration by intramuscular intravenous routes J

Antimicrob Chemother Dec 38(6) 969-76

7 Guerrini VH Filippich LJ Cao G R English PB Bourne DW (1985)

Pharmacokinetics of cefaronide ceftriaxone and cefperazone in sheep J Vet Pharmacol

Ther 8(2) 120-7

8 Swati Tiwari S Patel UD Bhavsar SK and Thaker AM (2010) Pharmacokinetics

and Bioavailability of Ceftriaxone in Patanwadi Sheep Online veterinary journal 5(2)

9 Ismail MM (2005) Pharmacokinetics urinary and mammary excretion of ceftriaxone in

lactating goats J Vet Med A Physiol Pathol Clin Med Sep 52(7) 354-8

10 Rajinder R prawez S Srivastiva AS (2005) Pharmacokinetics and dosage regimen of

ceftriaxone following its single ntramuscular adminsteration in kagani breed of goats

(Capra Hircus) Journal of reaserch 4(2) 91-93

11 Tiwari S Swati Bhavsar SK Patel UD and Thaker AM (2009) Disposition of

Ceftriaxone in Goats (Capra hircus) Online veterinary journal 4(2)

12 Dardi MS Sharma SK and Srivastava AK (2004) Pharmacokinetics and Dosage

regimen of ceftriaxone in buffalo calves Vet Res Commun 28 331-338

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Grouping of goats

Group (1)

It included 4 normal post-partum lactating goats Each goat was injected intravenously into

the left jugular vein ceftriaxone These goats were left for 15 days after the intravenous

injection to insure complete excretion of ceftriaxone from bodies of goats Then each goat

was injected intramuscularly into the gluteus medius muscle with the same dose of

ceftriaxone The aim of intramuscular injection to calculate the bioavailability of ceftriaxone

in normal goats

Group (2)

It included 4 normal post-partum lactating goats Each goat was injected intramuscularly into

the gluteus medius muscle with 20 mgkg bwt ceftriaxone for five consecutive days

Group (3)

It included 4 experimentally infected post-partum lactating goats with twenty four hours

peptone water culture of enterpathogen Salmonella typhimurium which were cultured on

nutrient agar plates for 24 hours then suspension of culture were collected by sterile saline

By opacity tube the required concentration of 2Χ109 micro-organismsml was obtained Each

of the four goats received orally a 10 ml suspension containing 2x109

organismml The

clinical symptoms of bacteraemia as fever and diarrhea appeared after 48-72 hours of

injection with Salmonella typhimurium suspension[17]

Each goat was injected

intramuscularly into the gluteus medius muscle with ceftriaxone per kilogram body weight

48 hours after experimental infection with samlonella Typhmurium for five consecutive days

Collection of samples

Blood samples

Blood samples were collected from right jugular vein following a single intravenous injection

of ceftriaxone in normal goats blood samples were collected after 5 min 10 min15 min 30

min 1 2 4 8 and 12 hours of administration Blood samples following the second third

fourth and fifth intramuscular doses were collected before and 10 min 15 min 050 1 2 4 8

and 12 hours post injection Blood samples taken from goats were allowed to clot and the

serum separated by centrifugation collected and divided in to two parts the first part was

used for assay of ceftriaxone and the second part was used for creatinine assay All serum

samples were stored at ndash 20degC until assay for ceftriaxone and creatinine

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Urine samples

The urine sample was taken by using rubber balloon catheter (Folatex No 4158512) The

goats were catheterized and bladder was evacuated before each experiment Following

injection of ceftriaxone (single intravenous single intramuscular and repeated intramuscular

administration) in goats (normal and experimentally infected) urine samples were taken after

025 050 1 2 4 8 12 24 and 48 hours of administrations Urine sample which was taken

at 025 h was discarded Urine samples from goats of group (1) group (2) group (3) were

collected and divided into two parts the first part was used for assay of ceftriaxone and the

second part was used for creatinine assay All urine samples were stored at - 20degC until assay

for ceftriaxone After the end of each experiment the urinary bladder was irrigated with 15

milliliters potassium permanganate solution 1 5000 as antiseptic agent

Milk samples

The udder was completely evacuated before drug administration and milk samples were

collected by hand stripping from both teats Following injection of ceftriaxone (single

intravenous single intramuscular and repeated intramuscular administration) in goats (normal

and experimentally infected) milk samples were taken after 050 1 2 4 8 12 24 and 48

hours of administrations Milk sample which was taken at 025 h was discarded The udder of

each goat in all groups was completely evacuated before drug administration and after each

milk samples Milk samples from goats of all groups were allowed to clot (by mixing equal

volumes of milk and 25 trichloroacetic acid) and centrifuged The skim milk was collected

and stored at ndash 20degC until assay for ceftriaxone

Analytical Procedure

Assay of ceftriaxone

Ceftriaxone was assayed in goats serum distalled water and goats milk by microbiological

method using agar well diffusion method by using of Escherichia coli ATCC (American

type culture collection 25922) as tested microorganism which was obtained from

Microbiological Department Animal Health Institute Doky Giza Egypt)[18]

Concentrations of ceftriaxone in biological fluids were determined by modification of the

agar ndash plate diffusion method[19]

using Escherichia coli ATCC25922 as assay organism and

Muller Hinton agar media

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Assay of samples

According to[20]

three plates were used for each sample Six pores were made three of them

were filled with reference concentration while the other three pores were filled with the

serum milk or urine samples in triplicate manner The plates were incubated at 37degC for 18

hours then the diameter of inhibitory zones were measured The diameter of inhibitory zones

of samples were corrected by using the zone diameter of the reference concentration in the

same manner as previously discussed either by addition or subtraction From the standard

curve the concentrations corresponding to the corrected values of the inhibitory zones were

obtained

Drug clearance

Clearance of the tested drug from the blood of goats was estimated according to the following

equation

Drug clearance10 kg b wt =

Drug concentration in urine (microgml) X rate of diuresis (mlmin) Body weight (Kg)

_________________________________________________________________

Drug concentration in serum (microgml) X 10

Assay of creatinine in serum and urine

Creatinine was assayed by[21]

and performed by kit manufactured by Diamond diagnostics

company

Creatinine clearance

The creatinine clearance (mlmin10 kgbwt) for goats was calculated by the following

equation

Creatinine clearance 10 kgbwt =

Creatinine concentration in urine (mgL) X rate of diuresis (mlmin) Body weight (Kg)

______________________________________________________________________

Creatinine concentration in serum (mgL) X 10

Pharmacokinetic analysis

The pharmacokinetic parameters were calculated by using Winonlin version 12 and other

parameters according to[2223]

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Statistical Analysis

The data were calculated as mean plusmn standard error All statistical analysis were carried out

according to[24]

using the scientific calculator CASIO fx 120

RESULTS

Following a single intravenous injection of 20 mg ceftriaxonekg bwt in normal goats

ceftriaxone could be detected therapeutically for 8 hours post intravenous injection The

serum concentration ndash time curve of ceftriaxone following intravenous injection showed that

the drug obeyed a two compartments open model (Figure 1) The disposition kinetics of

ceftriaxone following a single intravenous intramuscular injection were recorded in table (1)

Intramuscular injection of 20 mg ceftriaxone per kilogram body weight twice daily for five

consecutive days in normal and Salmonella typhimurium infected goats revealed a lower

significant serum ceftriaxone concentration after the first third fifth seventh ninth doses in

Salmonella typhimurium infected goats compared with normal goats The pharmacokinetic

parameters of ceftriaxone after repeated intramuscular injection in normal were compared to

those in Salmonella typhimurium infected goats (Table 2) and (Figure 2 amp 3)

The highest concentrations of ceftriaxone in milk were recorded 4 hours after each

intramuscular dose (Table 3) with a significant lower value in Salmonella typhimurium

infected goats compared with normal goats The calculated milkserum concentrations ratios

of ceftriaxone after repeated intramuscular injection (Table 4)

The amount of urine (mlmin) voided after repeated intramuscular injection of 20 mgkg bwt

Twice daily of ceftriaxone for five consecutive days in normal and experimentally

Salmonella typhimurium infected goats were recorded in table (5) The mean peak urine

concentrations of ceftriaxone (Table 6) were reached 2 hours after each intramuscular dose

with a lower significant concentration in Salmonella typhimurium infected goats compared

with normal goats Urineserum concentration ratios of ceftriaxone after repeated

intramuscular injection in normal and experimentally Salmonella typhimurium infected goats

were calculated and illustrated in table (7) Creatinine clearance (mlmin10 kg bwt)

expressing glomerular filtration rate from blood of goats was shown in table (8) The rate of

ceftriaxone clearance (mlmin10 kg bwt) from blood of goats was shown in table (9) The

ratio between ceftriaxone clearance and creatinine clearance was calculated and illustrated in

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

table (10) The data revealed a significant lower ratio in Salmonella typhimurium infected

goats compared with normal goats after the third fifth seventh ninth doses

Table (1) Pharmacokinetics parameters of ceftriaxone (μgml) following a single

intravenous and intramuscuer injection of 20 mgkg bwt in normal goats (n=4)

Intramusculer_

(XplusmnS E)

Intravenous_

(XplusmnS E) Unit Parameters

-------- 1213 plusmn321321 microgml Cdeg

4360plusmn12343 61390 plusmn330 microgml A

43440plusmn43660 636 plusmn43316 h-1

α

43433plusmn3340 43340 plusmn43442 H (α) 43 T

43420plusmn43233 4333plusmn131 h-1

K12

43446plusmn43400 43409plusmn231 h-1

K21

-------- 43440plusmn431 lkg Vdss

4321plusmn6340 43636plusmn1303 microgml B

434446plusmn43419 43443plusmn43136 h-1

β

43141plusmn39340 43411plusmn331 H t05(β))

4344plusmn43401 434440plusmn43409 lkgh Cl tot

-------- 1136plusmn2111300 microgmlh AUMC

-------- 43303 plusmn0314 H MRT

9300plusmn2439 30plusmn034330 microgmlh AUC

3392plusmn63329 -------- F

43436plusmn4361 -------- h-1

K01

43420plusmn3346 -------- h-1

T05(k01)

4342plusmn330 -------- H Tmax(calc))

43021plusmn04343 -------- μgml Cmax(calc)

Cdeg Drug concentration in the serum at zero time immediately after a single intravenous

injection (μgml) A amp B Zero time plasma drug concentration intercepts of biphasic

intravenous disposition curve The coefficient B is based on the terminal exponential phase

(μgml) α amp β Hybrid rate constant of biphasic intravenous disposition curve values of α

and β are related to the slopes of distribution and elimination phase respectively of

biexponential drug disposition curve (h-1

) T05 (α) Distribution half ndash life (h) t05 (β)

Elimination half ndash life (h) K12 First ndash order transfer rate constant for drug distribution from

Central to peripheral compartment (h-1

) K21 First order transfer rate constant for drug

distribution from Peripheral to central compartment (h-1

) Vdss The apparent volume of

distribution which was calculated by steady ndash state method (mlkg) AUMC Area under

moment curve MRT Mean residence time AUC Total area under the serum drug

concentration versus time curve from t = 0 to t = α after administration of a single dose F

Bioavailability Cmax maximum drug concentration Tmax time of maximum observed

concentration in blood

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Figure (1) Arthimatic plot of Serum concentrations of ceftriaxone (μgml) in normal

goats following a single intramuscular injection )diamsdiams( previously given the same doseby

a single intravenous injection () of 20 mg ceftriaxonekgbwt (n=4)

Figure (2) Semilogarthmic graph depicting the time course of ceftriaxone in serum of

normal goats following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt

twice dialy for five consecutive days (n=4)

Figure (3) Semilogarthmic graph depicting the time course of ceftriaxone in serum of

experimentally Salmonella typhimurim infected goats following repeated ntramuscular

injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4) 3

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Table (2) Pharmacokinetic parameters of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected

goats following repeated ntramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)

Dose

Unit

عىهParameters

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1269plusmn0073 7409plusmn121 1352plusmn0132 6373plusmn147 1410plusmn0243 5923plusmn126 1461plusmn0214 5430plusmn125 1424plusmn0172 7635plusmn176 gmlmicro A

0651plusmn0049 plusmn000843116 0720plusmn0008 plusmn00413300 0823plusmn0006 plusmn00263322 0848plusmn0025 plusmn00233323 0786plusmn0028 133plusmn0033 h-1 Α

106plusmn0008 330plusmn0015 0962plusmn0011 0392plusmn0007 0841plusmn0007 0567plusmn012 0818plusmn0024 0569plusmn0012 0885plusmn0030 plusmn00124322 H T05(α)

248plusmn0019 168plusmn0047 203plusmn0075 181plusmn0033 267plusmn0039 120plusmn0028 248plusmn0060 122plusmn0026 222plusmn0100 136plusmn0027 h-1 Kab

0278plusmn0002 0412plusmn0009 0342plusmn0012 0383plusmn0008 0252plusmn0009 0567plusmn0011 0279plusmn0005 00569plusmn0011 0314plusmn0014 0 510plusmn0012 H T05(ab)

0627plusmn0008 0378plusmn0007 0430plusmn0008 0402plusmn0008 0113plusmn00027 0424plusmn0009 0117plusmn0004 0394plusmn0008 0116plusmn0003 0239plusmn0005 h-1 K12

121plusmn0013 0962plusmn0022 141plusmn0021 130plusmn0023 0666plusmn0019 0651plusmn0013 0683plusmn0020 0660plusmn0013 0761plusmn0039 0998plusmn0023 h-1 K21

115plusmn0035 129plusmn0026 104plusmn0047 112plusmn0024 106plusmn0037 122plusmn0025 110plusmn0077 119plusmn0023 0910plusmn0032 123plusmn0023 H Tmax

4182plusmn0628 6108plusmn140 3440plusmn0363 5135plusmn0860 3117plusmn0965 4774plusmn0854 2713plusmn0781 4243plusmn0 870 2479plusmn0547 4065plusmn0825 gmlmicro Cmax

4944plusmn0820 7195plusmn142 4199plusmn0702 6511plusmn130 3190plusmn0688 5117plusmn113 3185plusmn0909 4709plusmn0990 3256plusmn0918 6329plusmn139 gmlmicro B

0164plusmn0003 0189plusmn00043 0181plusmn0002 0178plusmn0004 0181plusmn00035 0167plusmn0004 0214plusmn0009 0195plusmn0005 0249plusmn0918 0272plusmn0006 h-1 β

423plusmn0079 367plusmn0086 381plusmn0047 388plusmn0089 382plusmn0074 415plusmn0081 325plusmn0139 355plusmn0075 277plusmn0056 255plusmn0050 H T05β

0879plusmn0015 0429plusmn0009 109plusmn0004 0426plusmn0009 133plusmn0022 0503plusmn0011 154plusmn0064 0675plusmn0013 171plusmn0060 0693plusmn0014 Lkgh Cltot

28358plusmn215 40775plusmn808 21784plusmn0888 34259plusmn720 17860plusmn155 30705plusmn601 15281plusmn239 24135plusmn555 12175plusmn144 20292plusmn487 gmlhmicro AUC

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (3) Milk concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats

following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)

Dose Time of

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

197plusmn0205 200plusmn0408 125plusmn0104 155plusmn0132 0887plusmn0013 0885plusmn014 0500plusmn0040 074plusmn0012 ------------ ------ Before

200plusmn0408 22plusmn0108 197plusmn0205 200plusmn0408 155plusmn0132 197plusmn0205 100plusmn000 155plusmn0132 ----------- -------- 050

526plusmn0166 700plusmn0408 300plusmn0408 64plusmn0163 25plusmn0204 600plusmn0408 155plusmn0132 582plusmn0118 100plusmn000 520plusmn0166 1

640plusmn0163 900plusmn0408 582plusmn0118 792plusmn0114 582plusmn0118 755plusmn0221 275plusmn0061 700plusmn0408 200plusmn0408 691plusmn0176 2

900plusmn0408 1512plusmn0125 640plusmn0163 1475plusmn0322 640plusmn0163 1400plusmn0408 600plusmn0408 1352plusmn0205 526plusmn166 1225plusmn0595 4

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350plusmn0353 400plusmn0408 300plusmn0408 392plusmn0125 300plusmn0408 35plusmn0353 275plusmn006 300plusmn0408 155plusmn0132 275plusmn0061 6

300 plusmn0408 35plusmn0353 125plusmn0104 200plusmn0408 125plusmn0104 155plusmn01 0825plusmn0062 100plusmn000 0500plusmn0040 0887plusmn0013 8

200plusmn0408 22plusmn0108 100plusmn000 155plusmn0132 100plusmn000 125plusmn0104 0730plusmn002 0825plusmn0078 0422plusmn000 073plusmn0020 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (4) Milkserum concentrations ratios of ceftriaxone in normal and experimentally Salmonella typhimurim infected

goats following repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice daily for five consecutive days (n=4)

Dose Time of

a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

0400plusmn0049 025plusmn0063 0307plusmn0026 021plusmn0019 0365plusmn00064 016plusmn0026 0232plusmn0016 0205plusmn0002 -------- helliphelliphelliphellip Before

0057plusmn0125 0042plusmn00025 0062plusmn00062 0042plusmn0010 0575plusmn00062 0055plusmn0006 0067plusmn0016 0049plusmn0005 --------- -------- 050

0127plusmn00062 0115plusmn00064 008plusmn0012 0117plusmn0004 0088plusmn00054 0122plusmn0008 008plusmn0017 0126plusmn0028 0039plusmn0005 0122plusmn0004 1

018plusmn0008 0185plusmn0010 021plusmn0004 017plusmn0004 0182plusmn0054 0179plusmn0006 0112plusmn00025 0193plusmn0012 0097plusmn0020 019plusmn0004 2

0357plusmn0020 0425plusmn0005 033plusmn0021 045plusmn0009 0285plusmn0082 0494plusmn0015 0395plusmn0016 0572plusmn001 0415plusmn0017 054plusmn0027 4

018plusmn0015 016plusmn0016 0207plusmn0022 0175plusmn0006 0257plusmn0037 0180plusmn0017 0272plusmn0015 0201plusmn003 0196plusmn0016 0222plusmn0002 6

0212plusmn0033 0212plusmn0020 0200plusmn0044 0122plusmn0024 0152plusmn0011 014plusmn0022 0122plusmn00062 0102plusmn0001 0107plusmn00094 0117plusmn0002 8

0372plusmn0042 025plusmn001 0325plusmn0027 0192plusmn0014 0265plusmn00064 0185plusmn0015 0272plusmn0125 0195plusmn0012 0252plusmn0032 0275plusmn0009 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

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Table (5) The amount of urine (mlmin) voided in normal and experimentally Salmonella typhimurim infected goats following

repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)

Dose Time of a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

plusmn00372344 126plusmn0034 130plusmn0030 130plusmn0028 118plusmn0066 118plusmn0067 108plusmn0013 108plusmn0008 ----------- -------- Before

0577plusmn0069 43494057plusmn 045plusmn0060 plusmn0064309 0312plusmn002 033plusmn0012 0340plusmn0024 033plusmn0012 0287plusmn0017 0272plusmn0014 050

0712plusmn0019 0692plusmn0014 068plusmn0081 0697plusmn0006 0672plusmn0011 0675plusmn 0009 0635plusmn0032 0655plusmn0010 0719plusmn0031 0697plusmn0015 1

0837plusmn0025 0787plusmn0021 0732plusmn0011 plusmn00054300 0715plusmn0011 0715plusmn002 0722plusmn0019 0702plusmn0018 0737plusmn0027 0762plusmn0041 2

0535plusmn0095 0507plusmn0021 0447plusmn0022 0452plusmn002 0402plusmn0075 0405plusmn0011 0400plusmn0057 0397plusmn0009 0380plusmn0004 038plusmn001 4

0437plusmn00094 0432plusmn0008 0400plusmn0010 0405plusmn0002 0380plusmn0007 plusmn00044319 0372plusmn0047 037plusmn 0007 0350plusmn0005 0365plusmn0006 6

0397plusmn0028 0410plusmn0008 0380plusmn0012 0395plusmn0009 0355plusmn0086 0352plusmn0007 0340plusmn0004 0345plusmn0005 0302plusmn0004 0335plusmn0005 8

0385plusmn001 0380plusmn0010 0385plusmn00064 0380plusmn0008 0365plusmn0064 0367plusmn0004 0362plusmn0086 0372plusmn0106 0327plusmn0006 0362plusmn0016 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (6) Urine concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats

following repeated intramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)

Dose Time of a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1125plusmn150 1125plusmn15 735plusmn287 81plusmn324 183plusmn03 555plusmn798 37plusmn0811 1815plusmn43290 -------------- ------ Before

2415plusmn357 2625plusmn374 1695plusmn788 249plusmn574 10575plusmn64 2415plusmn357 5400plusmn273 2085plusmn991 102plusmn160 168plusmn547 050

26025plusmn787 2923plusmn479 22425plusmn1225 2805plusmn35 1695plusmn618 2705plusmn471 10200plusmn547 2415plusmn357 6975plusmn225 22425plusmn894 1

29295plusmn765 3012plusmn346 28575plusmn738 2964plusmn415 2355plusmn259 2923plusmn479 1635plusmn561 2645plusmn917 102plusmn547 24825plusmn616 2

23475plusmn430 2482plusmn616 23475plusmn1564 2415plusmn357 1695plusmn788 198plusmn848 8475plusmn309 1515plusmn708 60plusmn212 1185plusmn45 4

1905plusmn45 2355plusmn259 153plusmn519 1935plusmn960 114plusmn948 159plusmn173 6675plusmn309 1215plusmn45 1312plusmn0552 855plusmn193 6

153plusmn1024 1965plusmn135 1335plusmn1229 150plusmn34 735plusmn295 1365plusmn665 6181plusmn339 72plusmn244 907plusmn0951 5025plusmn143 8

135plusmn519 120plusmn346 11725plusmn1551 96plusmn874 525plusmn295 75plusmn173 153plusmn130 39plusmn212 3735plusmn0458 13125plusmn0552 12

Between normal and diseased

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Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (7) Urineserum concentrations ratios of ceftriaxone following repeated ntramuscular injection of 20 mg

ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats

(n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

229plusmn 163 1448plusmn0743 1885plusmn159 1125plusmn0484 533plusmn0260 1050plusmn358 175plusmn0380 4146plusmn116 ------- ------ Before

741plusmn0063 plusmn01553 58plusmn0242 plusmn0149390 422plusmn0206 683plusmn0106 245plusmn0092 667plusmn0306 0510plusmn0081 559plusmn0181 050

651plusmn0243 plusmn0065031 637plusmn0373 plusmn014431 565plusmn0243 plusmn0085300 360plusmn0303 plusmn0110312 279plusmn0121 534plusmn0248 1

836plusmn0150 plusmn00476322 862plusmn0180 plusmn010463 942plusmn0166 plusmn0130631 217plusmn0303 727plusmn0256 508plusmn0186 plusmn01680340 2

939plusmn0235 plusmn01580344 1006plusmn0710 plusmn00750310 999plusmn0542 plusmn02850344 565plusmn0223 641plusmn0241 48plusmn0164 plusmn014834 4

1005plusmn0418 2plusmn018813 1097plusmn0641 plusmn03979300 993plusmn0921 plusmn0252931 619plusmn0483 plusmn0362933 167plusmn0101 642plusmn0644 6

1091plusmn0649 plusmn075332339 1171plusmn0980 995plusmn0415 925plusmn0593 plusmn05593433 886plusmn0408 plusmn02510311 2055plusmn0311 plusmn02046310 8

2392plusmn129 plusmn032731396 1794plusmn0228 1222plusmn124 1418plusmn109 plusmn026733336 580plusmn0397 plusmn03951326 227plusmn0452 plusmn02740316 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (8) Creatinine clearance (mlmin10kgbwt) following repeated intramuscular injection of 20 mg ceftriaxonekgbwt

twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats (n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1115plusmn0703 2265plusmn167 481plusmn0409 672plusmn0817 669plusmn0672 1202plusmn0777 695plusmn0634 1724plusmn179 ----------- ------ Before

0703plusmn0091 147plusmn0305 0718plusmn0141 251plusmn0707 0547plusmn0055 0699plusmn0092 0802plusmn0099 103plusmn0106 295plusmn0124 0458plusmn0037 050

101plusmn0075 161plusmn0093 131plusmn0099 264plusmn0217 161plusmn0146 373plusmn0499 247plusmn0110 4755plusmn0582 214plusmn0234 103plusmn0166 1

157plusmn0198 387plusmn0340 173plusmn0501 267plusmn0217 187plusmn0563 287plusmn0499 451plusmn0223 972plusmn105 263plusmn0399 169plusmn0454 2

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184plusmn0095 346plusmn0444 173plusmn0501 436plusmn0599 383plusmn0299 682plusmn0584 328plusmn0253 119plusmn153 123plusmn0057 292plusmn0742 4

221plusmn0242 411plusmn0661 241plusmn0186 663plusmn0584 308plusmn0234 422plusmn0314 353plusmn0393 548plusmn0901 105plusmn0057 264plusmn0294 6

261plusmn0295 476plusmn0339 319plusmn0273 753plusmn0676 106plusmn0207 0773plusmn0049 228plusmn0175 456plusmn0340 206plusmn0160 404plusmn0419 8

310plusmn0218 409plusmn0434 3264plusmn0153 669plusmn0476 209plusmn0189 235plusmn0337 217plusmn0143 377plusmn0342 240plusmn0218 6055plusmn0176 12

Between normal and diseased

Plt 005 Plt001 Plt0001

Table (9) Ceftriaxone clearance (mlmin10kgbwt following repeated intramuscular injection of 20 mg ceftriaxone kgbwt

twice in normal and experimentally Salmonella typhimurim infected goats (n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1048plusmn121 0557plusmn684 895plusmn113 0547plusmn560 238plusmn0222 103plusmn 480 0668plusmn0157 0173plusmn216 -------- ----------- Before

156plusmn0251 43204plusmn3322 0936plusmn0162 43211plusmn3334 0473plusmn0037 43469plusmn43964 0300plusmn0028 43341plusmn080 0190plusmn0137 43400plusmn43642 050

166plusmn0079 43323plusmn3311 157plusmn0178 43419plusmn3301 137plusmn0115 43311plusmn33022 0883plusmn0054 43341plusmn 133 0616plusmn0153 43120plusmn3301 1

254plusmn0272 43361plusmn3391 222plusmn0093 4331plusmn3390 243plusmn0180 43209plusmn3309 183plusmn0149 43310plusmn2340 128plusmn0153 43312plusmn3390 2

181plusmn0136 43339plusmn3316 161plusmn0129 433plusmn3329 144plusmn0100 43412plusmn3349 0821plusmn0072 0063plusmn0977 0654plusmn0065 43400plusmn4306 4

160plusmn0177 43393plusmn336 152plusmn0200 43416plusmn331 135plusmn0118 4332plusmn3322 0897plusmn0052 43304plusmn3330 0212plusmn0022 43460plusmn43112 6

153plusmn0049 43291plusmn234 163plusmn0242 43346plusmn3300 0891plusmn0272 43306plusmn3310 108plusmn0071 43416plusmn04310 0229plusmn0046 43490plusmn43916 8

340plusmn0522 43214plusmn2341 249plusmn0150 43112plusmn3393 186plusmn0159 43320plusmn336 0773plusmn0094 43390plusmn 134 0264plusmn0043 43400plusmn 54369 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

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Table (10) Ceftriaxone clearancecreatinine clearance following repeated ntramuscular injection of 20 mg

ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats

(n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

0934plusmn0083 0305plusmn0013 183plusmn0116 0864plusmn0098 0358plusmn0018 0279plusmn0047 0099plusmn0020 0127plusmn0001 ------- ----------- Before

220plusmn0115 0819plusmn0044 131plusmn00414 0458plusmn0029 0876plusmn0063 126plusmn0068 0361plusmn0011 0813plusmn0031 0018plusmn0003 108plusmn0062 050

164plusmn0078 0818plusmn0029 118plusmn0068 0546plusmn0027 0858plusmn0052 0407plusmn0041 0331plusmn0009 0287plusmn0025 0324plusmn0011 0909plusmn0187 1

161plusmn0044 0488plusmn0005 232plusmn128 0329plusmn0027 169plusmn0464 0686plusmn0050 0409plusmn0020 0220plusmn0029 0512plusmn0077 266plusmn177 2

0933plusmn0024 0394plusmn0005 0948plusmn0062 0296plusmn0007 0381plusmn0027 0160plusmn0008 0235plusmn0014 0083plusmn0006 0528plusmn0028 0362plusmn0041 4

0726plusmn0018 0411plusmn0028 0639plusmn0066 0204plusmn0006 0446plusmn0034 0286plusmn0008 0238plusmn0019 0214plusmn0006 020plusmn0013 0382plusmn0028 6

0609plusmn0072 0425plusmn0036 0508plusmn0052 0192plusmn0009 0524plusmn0146 174plusmn0083 0477plusmn0015 0213plusmn00018 0109plusmn0185 0222plusmn0006 8

108plusmn0128 0496plusmn0012 0942plusmn0004 0265plusmn0030 0891plusmn0056 0706plusmn0103 0351plusmn0022 0354plusmn0018 0111plusmn0021 0098plusmn0018 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

DISCUSSION

In the present investigation intravenous injection of 20 mg ceftriaxonekgbwt in normal goats the drug showed high serum level

(92plusmn 0408 μgml) at 5 minutes post-injection then its concentration was decreased gradually till reached its minimum level (18

plusmn0816μgml) at 8hours post-injection

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In the present investigation the intravenous injection of 20 mg ceftriaxonekgbwt In normal

goats showed that the drug disposition best fitted a two-compartments- open model a

compartment of plasma and rapid equilibrating tissues and a deeper slower compartment

The obtained result is consistent with those reported for ceftriaxone in lactating goats[9]

lactating ewe[25]

domestic cat[15]

calves[26]

and patanwadi sheep[8]

Also this phenomenon is

in agreement with those reported for other cephalosporines as ceftazidime in a rabbit[27]

cefepime in dog and neonatal foals[28]

ewes[29]

ceftriaxone in goats[9]

cefipime in calves[30]

ceftiofur in cross-bred friesian cattle[31]

cefipime in calves[32]

ceftiofur in cows[33]

cefpirome

in cross-bred calves[3]

cefazidime in goats[35]

and cefquinome in sheep and goats[36]

cefipime

in chickens[37]

Ceftriaxone was distributed after intravenous injection with a distribution phase (α) equal to

656 per hour with a short distribution half ndash life [t05 (α)] equal to 0104 hour The shorter

distribution half-life of ceftriaxone in goats suggested the rapid distribution of the drug in

body tissue and fluid and that nearly similar to that recorded for ceftriaxone in lactating

goats(012 hour)[9]

for ceftriaxone in lactating ewes (0152 hour)[2]

and for ceftriaxone in

calves( 013hour)[26]

The rapid distribution of ceftriaxone in goats is supported by high rate constant of transfer of

the drug from central to peripheral compartment [K12 = 353 h-1

] as compared to the rate

constant of transfer of the drug from peripheral to central compartment [K21= 295 h-1

] This

value is nearly similar to those reported for cefotaxime in goats (K21=327 h-1

)[38]

On contrast

this value was higher than those recorded for ceftriaxone in lactating goats (K21=143 h-1

)[9]

in

lactating ewes (K21=125 h-1

)[25]

and in domestic cats (K21=154 h-1

)[15]

The apparent volume of distribution of ceftriaxone was (0355plusmn0004LKg) this value is

nearly similar to that recorded for cefaronide in sheep(039 LKg)[7]

cefotaxime in dog (048

lkg)[39]

in goat (051 lkg)

[40] for caphalexin in buffalo calves (041 Lkg)

[41] for cefipime in

ewes and calves (032 lkg) (043Lkg)[29]

and[30]

respectively For ceftriaxone in domestic

cats (057Lkg)[15]

in camel (032Lkg)[42]

On the other hand this result is differ than that

reported for cefotaxime in buffalo calves (117Lkg)[43]

High value of the volume of

distribution suggested extensive penetration power Drug with volume of distribution greater

than one literkilogram indicated wide distribution or extensive tissue binding or both[44]

The

apparent volume of distribution in the present study indicated moderate tissue penetrating

power This result agreed with[15]

for ceftriaxone in domestic cats

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

Ceftriaxone is eliminated in the current study following a single intravenous injection with

elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the

data recorded for ceftizoxime in goats (624hours)[45]

On contrast this value was longer than

that reported for ceftriaxone in lactating ewe (175hours)[25]

for cefaronide in sheep (17

hours)[7]

For cephalexin in buffulo calves (216hours)[41]

for ceftriaxone in healthy horse

(162hours)[46]

also this value is longer than that recorded for ceftriaxone in lactating goats

(144hours)[9]

for cefipime in goats (186hours)[47]

The rate of total body clearance of ceftriaxone following a single intravenous injection is

0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]

On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating

goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)

(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]

respectively

The variation in total body clearance might be attributed to specific interspecies variation

handling of the drug method used healthy status of the animal[48]

The difference between values calculated for pharmacokinetic parameters may be attributed

to animal species the drug formulation employed the age the size or sex o l lf the animal

or even inter individual variation and also due to method of analysis of the drug[49]

Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the

drug reached its peak serum concentrations after one hour of injection with value

of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12

hours post-injection The reported peak serum concentrations neerly similar to that reported

for cephalexin in buffulo calves (457 microgml)[41]

These results is differed than those reported

for ceftriaxone in cross breed calves (188 microgml at 30 min[16]

in Kangro breed of goats

(Capra Hircus) (2640 microgml at 20 min[10][50]

found after intramuscular administration of

ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher

than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]

The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time

(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats

(4932 microgml[47]

The reported maximum serum concentration (Cmax) is higher than that

reported for ceftriaxone in lactating goats(236 microgml)[9]

in lactating ewes (1722 microgml[25]

in

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

goats (2151 microgml)[11]

for cefquinome in camels (123 microgml)[51]

for ceftriaxone in calves

(1534 microgml)[26]

in patanwadi sheep (1553 microgml)[8]

for cefpirome in cattle (101 microgml)[52]

And for ceftiofur in chickens (2594 μgml)[37]

On the other hand the result was lower than

that reported by[6]

who observed the maximum serum concentration (Cmax) of ceftriaxone in

human after ntramuscular administration was (805 microgml) also it was lower than that

reported for ceftriaxone in dog (11510 microgml)[53]

in domestic cats (5440 microgml)[15]

and for

ceftazoxime in goats (8878 microgml)[45]

The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating

ewes by[25]

On contrast it is longer than those reported for ceftriaxone in dogs

(129hours)[53]

for ceftriaxone in lactating goats (07hours)[9]

also the result was longer than

that reported for ceftriaxone in domestic cats (033hours)[15]

in buffulo calves (05 hours)[13]

and for cefpirome in cattle (075hours)[52]

The reported [tmax] is shorter than those reported

for cefquinome in camels (425hours)[51]

in sheep and goats (261 and 262 hours)[36]

and for

ceftiofur in chickens (251 hours)[37]

The elimination half life [t05(β)]

following a single intramuscular administration was 1804 hours This value is nearly agreed

with that recorded for cefquinomein camels (1024hours)[52]

On contrast this result is longer

than that reported for cephalexin in buffalo calves (243hours)[41]

for ceftriaxone in lactating

ewes (177hours)[25]

in buffalo calves (438hours)[13]

in goats (203 hours)[11]

and for

cefipime in goats (165 hours)[47]

The rate of total body clearance of ceftriaxone following a single intramuscular injection is

0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves

(401Lkgh)[13]

in goats (304 Lkgh)[11]

and in sheep (222 Lkgh)[8]

Bioavailability is the fraction of the drug administered by non vascular rout that gains

accesses to the systemic circulation The obtained result revealed that the calculated systemic

bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves

(61)[54]

It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]

On the other

hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]

for ceftriaxone in goats (59)[11]

in calves (47)[55]

On contrast this value is lower than

those reported for cefotaxime in two cats 982 and 93)[57]

for cephradine in goats

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

(739)[58]

for ceftazidime in a rabbit (966)[27]

for ceftriaxone in lactating goats (85)[9]

in lactating ewes (836)[25]

in domestic cats 8572[15]

for cefipime in goats 8645[47]

for ceftriaxone in buffulo calves 702[13]

and for ceftiofur in chickens 8890[37]

Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium

infected goats twics dialy for five days revealed that the drug could be detected in a

therapeutic level for 12hours following repeated intramuscular administrations and exceeded

the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]

The relative higher serum concentrations of ceftriaxone after the last dose compared to the

first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12

hours intervals for five consecutive days These observations agreed with data reported by[36]

on comparing the data of serum levels of repeated intramuscular injections with first

intramuscular injection it was revealed that repeated intramuscular injections of cefquinome

have cumulative effect in both species sheep and goats

The obtained result is inconsistent with that reported by[56]

who found thatwhen cefotaxime

was administered repetitively in patients the ratio of maximal serum levels after the last dose

to those after the first dose demonstrated minimal accumulation of intact drug and by[60]

who

found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in

buffalo calves

The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium

infected goats are significantly lower than those in normal goats following repeated

intramuscular injection These lower blood concentrations in Salmonella typhimurium

infected goats might be attributed to the higher penetrating power of ceftriaxone to the

diseased tissues[48]

This phenomenon is similar to data recorded by[61]

who suggested that

Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of

ceftriaxone These alterations might be due to fever and inflammation induced by

infections[59]

proved that the serum concentrations of cephradine following intramuscular

administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after

each intramuscular dose with a lower significant values recorded in Escherichia-coli infected

goats than in normal goatsAlso similer to that reported by[62]

who observed that the

maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

in comparison to normal sheepOn contrast[43]

reported that peak plasma level of cefotaxime

in febrile buffalo calves was higher than healthy buffalo calves

In this study the total body clearance (CLtot) in normal goats are significantly lower than in

Salmonella typhimurium infected goats This result supported by[61]

and[63]

fever and

inflammation are cardinal features in bacterial infection which may in turn caused an

increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all

these could lead to increased in the rate at which the drug was delivered to both organs which

were important sites of drug excretion This might somewhat explain the increase in the total

body clearance in infected goats This result is differ than that reported by[64]

who observed

that the clearance of ceftriaxone was significantly reduced in infected mice than in non

infected animals

The highest concentrations of ceftriaxone in milk are recorded 4 hours after each

intramuscular injection with a significant lower value in Salmonella typhimurium infected

goats than in normal goats This might be attributed to accumulation of drug in the inflammed

tissues[48]

This result is similar to those reported by[6559]

who found that milk concentrations

of gentamicin and cephradine were significantly lower in infected goats and cattle than in

normal ones respectively

The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the

non-ionic passive diffusion principle[66]

reported that most drug cross-lipid membranes by

passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly

influenced by the physicochemical properties of the drug[6768]

Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum

ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the

physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]

Milk

contains substantially more lipid and less protein than serum and is slightly more acidic

Therefore drugs which tend to concentrated in milk are weak bases with low serum protein

binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide

and aminothiazole also possesses an hydroxytriazinone group as new and additional

ionization center[70]

these compounds are sufficiently lipid- soluble to be able to penetrate

tissues

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

The dose of ceftriaxone used in the present study induced therapeutically concentrations in

milk These concentrations suggested that ceftriaxone would be efficacious in treatment of

mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily

for 3-5 days

The study showed that the urine concentrations of ceftriaxone are greater than the concurrent

serum concentrations following intramuscular injection This observation is similar to those

reported in cows after cephapirin administrations[71]

In the present study urine concentrations of ceftriaxone increased with the repetition of

dosing This observation supported by[72]

after repeated intramuscular administrations of

ceftriaxone in healthy volunteeres

The mean peak urine concentrations of ceftriaxone were reached 2 hours after each

intramuscular injection The lower urine ceftriaxone concentrations in Salmonella

typhimurium infected goats than in normal goats might be attributed to the accumulation of

the drug in the inflamed tissues[48]

The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower

ratio in Salmonella typhimurium infected goats than in normal goats at different time of

sampling This indicates that glomerular filteration seemed to be the main pathway of

ceftriaxone elimination This observation supported by[59]

who found that the ratio between

cephradine clearance from blood of goats to creatinine clearance showed a marked decrease

in Escherichia-coli infected goats than in normal goats This indicated that glomerular

filteration seemed to be the main pathway of cephradine elimination with a limited rate of

tubular reabsorption

CONCLUSION

The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value

referred a better absorption of ceftriaxone from its site of intramuscular administration The

high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular

administrations suggested that ceftriaxone could be used for treatment of mastitis caused by

Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats

The high concentrations of ceftriaxone in urine after repeated intramuscular administrations

suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in

goats

REFERANCES

1 Neu HC Merpol NJ and Fukp (1981) Antibacterial activity of ceftriaxone

abetalactamase stable cephalosporines Antimicrobial agents and chemotherapy 19

414-423

2 Richard DM Heel RC Brogden RN Speight TM Avery GS (1984) Ceftriaxone a

review of its antibacterial activity pharmacological properties and therapeutic uses

Drugs 27 469-527

3 Brogden RN and Ward A (1988) Ceftriaxone a reappraisal of its antibacterial activity

and pharmacokinetic properties and an update on its therapeutic use with particular

reference to once-daily administration Drugs 35 604-645

4 Waxman DJ and Strominger JL (1983) Penicillin-binding proteins and the

mechanism of action of beta-lactam antibiotics Annu Rev Biochem 52(1) 825-869

5 Christ W (1991) properties of cephalosporines Infestion 19 244-252

6 Goonetilleke AK Dev D Aziz I Hughes C Smith MJ Basran GS (1996) A

comparative analysis of pharmacokinetics of ceftriaxone in serum and pleural fluid in

humans a study of once daily administration by intramuscular intravenous routes J

Antimicrob Chemother Dec 38(6) 969-76

7 Guerrini VH Filippich LJ Cao G R English PB Bourne DW (1985)

Pharmacokinetics of cefaronide ceftriaxone and cefperazone in sheep J Vet Pharmacol

Ther 8(2) 120-7

8 Swati Tiwari S Patel UD Bhavsar SK and Thaker AM (2010) Pharmacokinetics

and Bioavailability of Ceftriaxone in Patanwadi Sheep Online veterinary journal 5(2)

9 Ismail MM (2005) Pharmacokinetics urinary and mammary excretion of ceftriaxone in

lactating goats J Vet Med A Physiol Pathol Clin Med Sep 52(7) 354-8

10 Rajinder R prawez S Srivastiva AS (2005) Pharmacokinetics and dosage regimen of

ceftriaxone following its single ntramuscular adminsteration in kagani breed of goats

(Capra Hircus) Journal of reaserch 4(2) 91-93

11 Tiwari S Swati Bhavsar SK Patel UD and Thaker AM (2009) Disposition of

Ceftriaxone in Goats (Capra hircus) Online veterinary journal 4(2)

12 Dardi MS Sharma SK and Srivastava AK (2004) Pharmacokinetics and Dosage

regimen of ceftriaxone in buffalo calves Vet Res Commun 28 331-338

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Urine samples

The urine sample was taken by using rubber balloon catheter (Folatex No 4158512) The

goats were catheterized and bladder was evacuated before each experiment Following

injection of ceftriaxone (single intravenous single intramuscular and repeated intramuscular

administration) in goats (normal and experimentally infected) urine samples were taken after

025 050 1 2 4 8 12 24 and 48 hours of administrations Urine sample which was taken

at 025 h was discarded Urine samples from goats of group (1) group (2) group (3) were

collected and divided into two parts the first part was used for assay of ceftriaxone and the

second part was used for creatinine assay All urine samples were stored at - 20degC until assay

for ceftriaxone After the end of each experiment the urinary bladder was irrigated with 15

milliliters potassium permanganate solution 1 5000 as antiseptic agent

Milk samples

The udder was completely evacuated before drug administration and milk samples were

collected by hand stripping from both teats Following injection of ceftriaxone (single

intravenous single intramuscular and repeated intramuscular administration) in goats (normal

and experimentally infected) milk samples were taken after 050 1 2 4 8 12 24 and 48

hours of administrations Milk sample which was taken at 025 h was discarded The udder of

each goat in all groups was completely evacuated before drug administration and after each

milk samples Milk samples from goats of all groups were allowed to clot (by mixing equal

volumes of milk and 25 trichloroacetic acid) and centrifuged The skim milk was collected

and stored at ndash 20degC until assay for ceftriaxone

Analytical Procedure

Assay of ceftriaxone

Ceftriaxone was assayed in goats serum distalled water and goats milk by microbiological

method using agar well diffusion method by using of Escherichia coli ATCC (American

type culture collection 25922) as tested microorganism which was obtained from

Microbiological Department Animal Health Institute Doky Giza Egypt)[18]

Concentrations of ceftriaxone in biological fluids were determined by modification of the

agar ndash plate diffusion method[19]

using Escherichia coli ATCC25922 as assay organism and

Muller Hinton agar media

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Assay of samples

According to[20]

three plates were used for each sample Six pores were made three of them

were filled with reference concentration while the other three pores were filled with the

serum milk or urine samples in triplicate manner The plates were incubated at 37degC for 18

hours then the diameter of inhibitory zones were measured The diameter of inhibitory zones

of samples were corrected by using the zone diameter of the reference concentration in the

same manner as previously discussed either by addition or subtraction From the standard

curve the concentrations corresponding to the corrected values of the inhibitory zones were

obtained

Drug clearance

Clearance of the tested drug from the blood of goats was estimated according to the following

equation

Drug clearance10 kg b wt =

Drug concentration in urine (microgml) X rate of diuresis (mlmin) Body weight (Kg)

_________________________________________________________________

Drug concentration in serum (microgml) X 10

Assay of creatinine in serum and urine

Creatinine was assayed by[21]

and performed by kit manufactured by Diamond diagnostics

company

Creatinine clearance

The creatinine clearance (mlmin10 kgbwt) for goats was calculated by the following

equation

Creatinine clearance 10 kgbwt =

Creatinine concentration in urine (mgL) X rate of diuresis (mlmin) Body weight (Kg)

______________________________________________________________________

Creatinine concentration in serum (mgL) X 10

Pharmacokinetic analysis

The pharmacokinetic parameters were calculated by using Winonlin version 12 and other

parameters according to[2223]

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Statistical Analysis

The data were calculated as mean plusmn standard error All statistical analysis were carried out

according to[24]

using the scientific calculator CASIO fx 120

RESULTS

Following a single intravenous injection of 20 mg ceftriaxonekg bwt in normal goats

ceftriaxone could be detected therapeutically for 8 hours post intravenous injection The

serum concentration ndash time curve of ceftriaxone following intravenous injection showed that

the drug obeyed a two compartments open model (Figure 1) The disposition kinetics of

ceftriaxone following a single intravenous intramuscular injection were recorded in table (1)

Intramuscular injection of 20 mg ceftriaxone per kilogram body weight twice daily for five

consecutive days in normal and Salmonella typhimurium infected goats revealed a lower

significant serum ceftriaxone concentration after the first third fifth seventh ninth doses in

Salmonella typhimurium infected goats compared with normal goats The pharmacokinetic

parameters of ceftriaxone after repeated intramuscular injection in normal were compared to

those in Salmonella typhimurium infected goats (Table 2) and (Figure 2 amp 3)

The highest concentrations of ceftriaxone in milk were recorded 4 hours after each

intramuscular dose (Table 3) with a significant lower value in Salmonella typhimurium

infected goats compared with normal goats The calculated milkserum concentrations ratios

of ceftriaxone after repeated intramuscular injection (Table 4)

The amount of urine (mlmin) voided after repeated intramuscular injection of 20 mgkg bwt

Twice daily of ceftriaxone for five consecutive days in normal and experimentally

Salmonella typhimurium infected goats were recorded in table (5) The mean peak urine

concentrations of ceftriaxone (Table 6) were reached 2 hours after each intramuscular dose

with a lower significant concentration in Salmonella typhimurium infected goats compared

with normal goats Urineserum concentration ratios of ceftriaxone after repeated

intramuscular injection in normal and experimentally Salmonella typhimurium infected goats

were calculated and illustrated in table (7) Creatinine clearance (mlmin10 kg bwt)

expressing glomerular filtration rate from blood of goats was shown in table (8) The rate of

ceftriaxone clearance (mlmin10 kg bwt) from blood of goats was shown in table (9) The

ratio between ceftriaxone clearance and creatinine clearance was calculated and illustrated in

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

table (10) The data revealed a significant lower ratio in Salmonella typhimurium infected

goats compared with normal goats after the third fifth seventh ninth doses

Table (1) Pharmacokinetics parameters of ceftriaxone (μgml) following a single

intravenous and intramuscuer injection of 20 mgkg bwt in normal goats (n=4)

Intramusculer_

(XplusmnS E)

Intravenous_

(XplusmnS E) Unit Parameters

-------- 1213 plusmn321321 microgml Cdeg

4360plusmn12343 61390 plusmn330 microgml A

43440plusmn43660 636 plusmn43316 h-1

α

43433plusmn3340 43340 plusmn43442 H (α) 43 T

43420plusmn43233 4333plusmn131 h-1

K12

43446plusmn43400 43409plusmn231 h-1

K21

-------- 43440plusmn431 lkg Vdss

4321plusmn6340 43636plusmn1303 microgml B

434446plusmn43419 43443plusmn43136 h-1

β

43141plusmn39340 43411plusmn331 H t05(β))

4344plusmn43401 434440plusmn43409 lkgh Cl tot

-------- 1136plusmn2111300 microgmlh AUMC

-------- 43303 plusmn0314 H MRT

9300plusmn2439 30plusmn034330 microgmlh AUC

3392plusmn63329 -------- F

43436plusmn4361 -------- h-1

K01

43420plusmn3346 -------- h-1

T05(k01)

4342plusmn330 -------- H Tmax(calc))

43021plusmn04343 -------- μgml Cmax(calc)

Cdeg Drug concentration in the serum at zero time immediately after a single intravenous

injection (μgml) A amp B Zero time plasma drug concentration intercepts of biphasic

intravenous disposition curve The coefficient B is based on the terminal exponential phase

(μgml) α amp β Hybrid rate constant of biphasic intravenous disposition curve values of α

and β are related to the slopes of distribution and elimination phase respectively of

biexponential drug disposition curve (h-1

) T05 (α) Distribution half ndash life (h) t05 (β)

Elimination half ndash life (h) K12 First ndash order transfer rate constant for drug distribution from

Central to peripheral compartment (h-1

) K21 First order transfer rate constant for drug

distribution from Peripheral to central compartment (h-1

) Vdss The apparent volume of

distribution which was calculated by steady ndash state method (mlkg) AUMC Area under

moment curve MRT Mean residence time AUC Total area under the serum drug

concentration versus time curve from t = 0 to t = α after administration of a single dose F

Bioavailability Cmax maximum drug concentration Tmax time of maximum observed

concentration in blood

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Figure (1) Arthimatic plot of Serum concentrations of ceftriaxone (μgml) in normal

goats following a single intramuscular injection )diamsdiams( previously given the same doseby

a single intravenous injection () of 20 mg ceftriaxonekgbwt (n=4)

Figure (2) Semilogarthmic graph depicting the time course of ceftriaxone in serum of

normal goats following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt

twice dialy for five consecutive days (n=4)

Figure (3) Semilogarthmic graph depicting the time course of ceftriaxone in serum of

experimentally Salmonella typhimurim infected goats following repeated ntramuscular

injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4) 3

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Table (2) Pharmacokinetic parameters of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected

goats following repeated ntramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)

Dose

Unit

عىهParameters

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1269plusmn0073 7409plusmn121 1352plusmn0132 6373plusmn147 1410plusmn0243 5923plusmn126 1461plusmn0214 5430plusmn125 1424plusmn0172 7635plusmn176 gmlmicro A

0651plusmn0049 plusmn000843116 0720plusmn0008 plusmn00413300 0823plusmn0006 plusmn00263322 0848plusmn0025 plusmn00233323 0786plusmn0028 133plusmn0033 h-1 Α

106plusmn0008 330plusmn0015 0962plusmn0011 0392plusmn0007 0841plusmn0007 0567plusmn012 0818plusmn0024 0569plusmn0012 0885plusmn0030 plusmn00124322 H T05(α)

248plusmn0019 168plusmn0047 203plusmn0075 181plusmn0033 267plusmn0039 120plusmn0028 248plusmn0060 122plusmn0026 222plusmn0100 136plusmn0027 h-1 Kab

0278plusmn0002 0412plusmn0009 0342plusmn0012 0383plusmn0008 0252plusmn0009 0567plusmn0011 0279plusmn0005 00569plusmn0011 0314plusmn0014 0 510plusmn0012 H T05(ab)

0627plusmn0008 0378plusmn0007 0430plusmn0008 0402plusmn0008 0113plusmn00027 0424plusmn0009 0117plusmn0004 0394plusmn0008 0116plusmn0003 0239plusmn0005 h-1 K12

121plusmn0013 0962plusmn0022 141plusmn0021 130plusmn0023 0666plusmn0019 0651plusmn0013 0683plusmn0020 0660plusmn0013 0761plusmn0039 0998plusmn0023 h-1 K21

115plusmn0035 129plusmn0026 104plusmn0047 112plusmn0024 106plusmn0037 122plusmn0025 110plusmn0077 119plusmn0023 0910plusmn0032 123plusmn0023 H Tmax

4182plusmn0628 6108plusmn140 3440plusmn0363 5135plusmn0860 3117plusmn0965 4774plusmn0854 2713plusmn0781 4243plusmn0 870 2479plusmn0547 4065plusmn0825 gmlmicro Cmax

4944plusmn0820 7195plusmn142 4199plusmn0702 6511plusmn130 3190plusmn0688 5117plusmn113 3185plusmn0909 4709plusmn0990 3256plusmn0918 6329plusmn139 gmlmicro B

0164plusmn0003 0189plusmn00043 0181plusmn0002 0178plusmn0004 0181plusmn00035 0167plusmn0004 0214plusmn0009 0195plusmn0005 0249plusmn0918 0272plusmn0006 h-1 β

423plusmn0079 367plusmn0086 381plusmn0047 388plusmn0089 382plusmn0074 415plusmn0081 325plusmn0139 355plusmn0075 277plusmn0056 255plusmn0050 H T05β

0879plusmn0015 0429plusmn0009 109plusmn0004 0426plusmn0009 133plusmn0022 0503plusmn0011 154plusmn0064 0675plusmn0013 171plusmn0060 0693plusmn0014 Lkgh Cltot

28358plusmn215 40775plusmn808 21784plusmn0888 34259plusmn720 17860plusmn155 30705plusmn601 15281plusmn239 24135plusmn555 12175plusmn144 20292plusmn487 gmlhmicro AUC

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (3) Milk concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats

following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)

Dose Time of

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

197plusmn0205 200plusmn0408 125plusmn0104 155plusmn0132 0887plusmn0013 0885plusmn014 0500plusmn0040 074plusmn0012 ------------ ------ Before

200plusmn0408 22plusmn0108 197plusmn0205 200plusmn0408 155plusmn0132 197plusmn0205 100plusmn000 155plusmn0132 ----------- -------- 050

526plusmn0166 700plusmn0408 300plusmn0408 64plusmn0163 25plusmn0204 600plusmn0408 155plusmn0132 582plusmn0118 100plusmn000 520plusmn0166 1

640plusmn0163 900plusmn0408 582plusmn0118 792plusmn0114 582plusmn0118 755plusmn0221 275plusmn0061 700plusmn0408 200plusmn0408 691plusmn0176 2

900plusmn0408 1512plusmn0125 640plusmn0163 1475plusmn0322 640plusmn0163 1400plusmn0408 600plusmn0408 1352plusmn0205 526plusmn166 1225plusmn0595 4

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

350plusmn0353 400plusmn0408 300plusmn0408 392plusmn0125 300plusmn0408 35plusmn0353 275plusmn006 300plusmn0408 155plusmn0132 275plusmn0061 6

300 plusmn0408 35plusmn0353 125plusmn0104 200plusmn0408 125plusmn0104 155plusmn01 0825plusmn0062 100plusmn000 0500plusmn0040 0887plusmn0013 8

200plusmn0408 22plusmn0108 100plusmn000 155plusmn0132 100plusmn000 125plusmn0104 0730plusmn002 0825plusmn0078 0422plusmn000 073plusmn0020 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (4) Milkserum concentrations ratios of ceftriaxone in normal and experimentally Salmonella typhimurim infected

goats following repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice daily for five consecutive days (n=4)

Dose Time of

a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

0400plusmn0049 025plusmn0063 0307plusmn0026 021plusmn0019 0365plusmn00064 016plusmn0026 0232plusmn0016 0205plusmn0002 -------- helliphelliphelliphellip Before

0057plusmn0125 0042plusmn00025 0062plusmn00062 0042plusmn0010 0575plusmn00062 0055plusmn0006 0067plusmn0016 0049plusmn0005 --------- -------- 050

0127plusmn00062 0115plusmn00064 008plusmn0012 0117plusmn0004 0088plusmn00054 0122plusmn0008 008plusmn0017 0126plusmn0028 0039plusmn0005 0122plusmn0004 1

018plusmn0008 0185plusmn0010 021plusmn0004 017plusmn0004 0182plusmn0054 0179plusmn0006 0112plusmn00025 0193plusmn0012 0097plusmn0020 019plusmn0004 2

0357plusmn0020 0425plusmn0005 033plusmn0021 045plusmn0009 0285plusmn0082 0494plusmn0015 0395plusmn0016 0572plusmn001 0415plusmn0017 054plusmn0027 4

018plusmn0015 016plusmn0016 0207plusmn0022 0175plusmn0006 0257plusmn0037 0180plusmn0017 0272plusmn0015 0201plusmn003 0196plusmn0016 0222plusmn0002 6

0212plusmn0033 0212plusmn0020 0200plusmn0044 0122plusmn0024 0152plusmn0011 014plusmn0022 0122plusmn00062 0102plusmn0001 0107plusmn00094 0117plusmn0002 8

0372plusmn0042 025plusmn001 0325plusmn0027 0192plusmn0014 0265plusmn00064 0185plusmn0015 0272plusmn0125 0195plusmn0012 0252plusmn0032 0275plusmn0009 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

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Table (5) The amount of urine (mlmin) voided in normal and experimentally Salmonella typhimurim infected goats following

repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)

Dose Time of a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

plusmn00372344 126plusmn0034 130plusmn0030 130plusmn0028 118plusmn0066 118plusmn0067 108plusmn0013 108plusmn0008 ----------- -------- Before

0577plusmn0069 43494057plusmn 045plusmn0060 plusmn0064309 0312plusmn002 033plusmn0012 0340plusmn0024 033plusmn0012 0287plusmn0017 0272plusmn0014 050

0712plusmn0019 0692plusmn0014 068plusmn0081 0697plusmn0006 0672plusmn0011 0675plusmn 0009 0635plusmn0032 0655plusmn0010 0719plusmn0031 0697plusmn0015 1

0837plusmn0025 0787plusmn0021 0732plusmn0011 plusmn00054300 0715plusmn0011 0715plusmn002 0722plusmn0019 0702plusmn0018 0737plusmn0027 0762plusmn0041 2

0535plusmn0095 0507plusmn0021 0447plusmn0022 0452plusmn002 0402plusmn0075 0405plusmn0011 0400plusmn0057 0397plusmn0009 0380plusmn0004 038plusmn001 4

0437plusmn00094 0432plusmn0008 0400plusmn0010 0405plusmn0002 0380plusmn0007 plusmn00044319 0372plusmn0047 037plusmn 0007 0350plusmn0005 0365plusmn0006 6

0397plusmn0028 0410plusmn0008 0380plusmn0012 0395plusmn0009 0355plusmn0086 0352plusmn0007 0340plusmn0004 0345plusmn0005 0302plusmn0004 0335plusmn0005 8

0385plusmn001 0380plusmn0010 0385plusmn00064 0380plusmn0008 0365plusmn0064 0367plusmn0004 0362plusmn0086 0372plusmn0106 0327plusmn0006 0362plusmn0016 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (6) Urine concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats

following repeated intramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)

Dose Time of a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1125plusmn150 1125plusmn15 735plusmn287 81plusmn324 183plusmn03 555plusmn798 37plusmn0811 1815plusmn43290 -------------- ------ Before

2415plusmn357 2625plusmn374 1695plusmn788 249plusmn574 10575plusmn64 2415plusmn357 5400plusmn273 2085plusmn991 102plusmn160 168plusmn547 050

26025plusmn787 2923plusmn479 22425plusmn1225 2805plusmn35 1695plusmn618 2705plusmn471 10200plusmn547 2415plusmn357 6975plusmn225 22425plusmn894 1

29295plusmn765 3012plusmn346 28575plusmn738 2964plusmn415 2355plusmn259 2923plusmn479 1635plusmn561 2645plusmn917 102plusmn547 24825plusmn616 2

23475plusmn430 2482plusmn616 23475plusmn1564 2415plusmn357 1695plusmn788 198plusmn848 8475plusmn309 1515plusmn708 60plusmn212 1185plusmn45 4

1905plusmn45 2355plusmn259 153plusmn519 1935plusmn960 114plusmn948 159plusmn173 6675plusmn309 1215plusmn45 1312plusmn0552 855plusmn193 6

153plusmn1024 1965plusmn135 1335plusmn1229 150plusmn34 735plusmn295 1365plusmn665 6181plusmn339 72plusmn244 907plusmn0951 5025plusmn143 8

135plusmn519 120plusmn346 11725plusmn1551 96plusmn874 525plusmn295 75plusmn173 153plusmn130 39plusmn212 3735plusmn0458 13125plusmn0552 12

Between normal and diseased

wwwwjppscom Vol 5 Issue 02 2016

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (7) Urineserum concentrations ratios of ceftriaxone following repeated ntramuscular injection of 20 mg

ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats

(n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

229plusmn 163 1448plusmn0743 1885plusmn159 1125plusmn0484 533plusmn0260 1050plusmn358 175plusmn0380 4146plusmn116 ------- ------ Before

741plusmn0063 plusmn01553 58plusmn0242 plusmn0149390 422plusmn0206 683plusmn0106 245plusmn0092 667plusmn0306 0510plusmn0081 559plusmn0181 050

651plusmn0243 plusmn0065031 637plusmn0373 plusmn014431 565plusmn0243 plusmn0085300 360plusmn0303 plusmn0110312 279plusmn0121 534plusmn0248 1

836plusmn0150 plusmn00476322 862plusmn0180 plusmn010463 942plusmn0166 plusmn0130631 217plusmn0303 727plusmn0256 508plusmn0186 plusmn01680340 2

939plusmn0235 plusmn01580344 1006plusmn0710 plusmn00750310 999plusmn0542 plusmn02850344 565plusmn0223 641plusmn0241 48plusmn0164 plusmn014834 4

1005plusmn0418 2plusmn018813 1097plusmn0641 plusmn03979300 993plusmn0921 plusmn0252931 619plusmn0483 plusmn0362933 167plusmn0101 642plusmn0644 6

1091plusmn0649 plusmn075332339 1171plusmn0980 995plusmn0415 925plusmn0593 plusmn05593433 886plusmn0408 plusmn02510311 2055plusmn0311 plusmn02046310 8

2392plusmn129 plusmn032731396 1794plusmn0228 1222plusmn124 1418plusmn109 plusmn026733336 580plusmn0397 plusmn03951326 227plusmn0452 plusmn02740316 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (8) Creatinine clearance (mlmin10kgbwt) following repeated intramuscular injection of 20 mg ceftriaxonekgbwt

twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats (n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1115plusmn0703 2265plusmn167 481plusmn0409 672plusmn0817 669plusmn0672 1202plusmn0777 695plusmn0634 1724plusmn179 ----------- ------ Before

0703plusmn0091 147plusmn0305 0718plusmn0141 251plusmn0707 0547plusmn0055 0699plusmn0092 0802plusmn0099 103plusmn0106 295plusmn0124 0458plusmn0037 050

101plusmn0075 161plusmn0093 131plusmn0099 264plusmn0217 161plusmn0146 373plusmn0499 247plusmn0110 4755plusmn0582 214plusmn0234 103plusmn0166 1

157plusmn0198 387plusmn0340 173plusmn0501 267plusmn0217 187plusmn0563 287plusmn0499 451plusmn0223 972plusmn105 263plusmn0399 169plusmn0454 2

wwwwjppscom Vol 5 Issue 02 2016

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

184plusmn0095 346plusmn0444 173plusmn0501 436plusmn0599 383plusmn0299 682plusmn0584 328plusmn0253 119plusmn153 123plusmn0057 292plusmn0742 4

221plusmn0242 411plusmn0661 241plusmn0186 663plusmn0584 308plusmn0234 422plusmn0314 353plusmn0393 548plusmn0901 105plusmn0057 264plusmn0294 6

261plusmn0295 476plusmn0339 319plusmn0273 753plusmn0676 106plusmn0207 0773plusmn0049 228plusmn0175 456plusmn0340 206plusmn0160 404plusmn0419 8

310plusmn0218 409plusmn0434 3264plusmn0153 669plusmn0476 209plusmn0189 235plusmn0337 217plusmn0143 377plusmn0342 240plusmn0218 6055plusmn0176 12

Between normal and diseased

Plt 005 Plt001 Plt0001

Table (9) Ceftriaxone clearance (mlmin10kgbwt following repeated intramuscular injection of 20 mg ceftriaxone kgbwt

twice in normal and experimentally Salmonella typhimurim infected goats (n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1048plusmn121 0557plusmn684 895plusmn113 0547plusmn560 238plusmn0222 103plusmn 480 0668plusmn0157 0173plusmn216 -------- ----------- Before

156plusmn0251 43204plusmn3322 0936plusmn0162 43211plusmn3334 0473plusmn0037 43469plusmn43964 0300plusmn0028 43341plusmn080 0190plusmn0137 43400plusmn43642 050

166plusmn0079 43323plusmn3311 157plusmn0178 43419plusmn3301 137plusmn0115 43311plusmn33022 0883plusmn0054 43341plusmn 133 0616plusmn0153 43120plusmn3301 1

254plusmn0272 43361plusmn3391 222plusmn0093 4331plusmn3390 243plusmn0180 43209plusmn3309 183plusmn0149 43310plusmn2340 128plusmn0153 43312plusmn3390 2

181plusmn0136 43339plusmn3316 161plusmn0129 433plusmn3329 144plusmn0100 43412plusmn3349 0821plusmn0072 0063plusmn0977 0654plusmn0065 43400plusmn4306 4

160plusmn0177 43393plusmn336 152plusmn0200 43416plusmn331 135plusmn0118 4332plusmn3322 0897plusmn0052 43304plusmn3330 0212plusmn0022 43460plusmn43112 6

153plusmn0049 43291plusmn234 163plusmn0242 43346plusmn3300 0891plusmn0272 43306plusmn3310 108plusmn0071 43416plusmn04310 0229plusmn0046 43490plusmn43916 8

340plusmn0522 43214plusmn2341 249plusmn0150 43112plusmn3393 186plusmn0159 43320plusmn336 0773plusmn0094 43390plusmn 134 0264plusmn0043 43400plusmn 54369 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Table (10) Ceftriaxone clearancecreatinine clearance following repeated ntramuscular injection of 20 mg

ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats

(n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

0934plusmn0083 0305plusmn0013 183plusmn0116 0864plusmn0098 0358plusmn0018 0279plusmn0047 0099plusmn0020 0127plusmn0001 ------- ----------- Before

220plusmn0115 0819plusmn0044 131plusmn00414 0458plusmn0029 0876plusmn0063 126plusmn0068 0361plusmn0011 0813plusmn0031 0018plusmn0003 108plusmn0062 050

164plusmn0078 0818plusmn0029 118plusmn0068 0546plusmn0027 0858plusmn0052 0407plusmn0041 0331plusmn0009 0287plusmn0025 0324plusmn0011 0909plusmn0187 1

161plusmn0044 0488plusmn0005 232plusmn128 0329plusmn0027 169plusmn0464 0686plusmn0050 0409plusmn0020 0220plusmn0029 0512plusmn0077 266plusmn177 2

0933plusmn0024 0394plusmn0005 0948plusmn0062 0296plusmn0007 0381plusmn0027 0160plusmn0008 0235plusmn0014 0083plusmn0006 0528plusmn0028 0362plusmn0041 4

0726plusmn0018 0411plusmn0028 0639plusmn0066 0204plusmn0006 0446plusmn0034 0286plusmn0008 0238plusmn0019 0214plusmn0006 020plusmn0013 0382plusmn0028 6

0609plusmn0072 0425plusmn0036 0508plusmn0052 0192plusmn0009 0524plusmn0146 174plusmn0083 0477plusmn0015 0213plusmn00018 0109plusmn0185 0222plusmn0006 8

108plusmn0128 0496plusmn0012 0942plusmn0004 0265plusmn0030 0891plusmn0056 0706plusmn0103 0351plusmn0022 0354plusmn0018 0111plusmn0021 0098plusmn0018 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

DISCUSSION

In the present investigation intravenous injection of 20 mg ceftriaxonekgbwt in normal goats the drug showed high serum level

(92plusmn 0408 μgml) at 5 minutes post-injection then its concentration was decreased gradually till reached its minimum level (18

plusmn0816μgml) at 8hours post-injection

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In the present investigation the intravenous injection of 20 mg ceftriaxonekgbwt In normal

goats showed that the drug disposition best fitted a two-compartments- open model a

compartment of plasma and rapid equilibrating tissues and a deeper slower compartment

The obtained result is consistent with those reported for ceftriaxone in lactating goats[9]

lactating ewe[25]

domestic cat[15]

calves[26]

and patanwadi sheep[8]

Also this phenomenon is

in agreement with those reported for other cephalosporines as ceftazidime in a rabbit[27]

cefepime in dog and neonatal foals[28]

ewes[29]

ceftriaxone in goats[9]

cefipime in calves[30]

ceftiofur in cross-bred friesian cattle[31]

cefipime in calves[32]

ceftiofur in cows[33]

cefpirome

in cross-bred calves[3]

cefazidime in goats[35]

and cefquinome in sheep and goats[36]

cefipime

in chickens[37]

Ceftriaxone was distributed after intravenous injection with a distribution phase (α) equal to

656 per hour with a short distribution half ndash life [t05 (α)] equal to 0104 hour The shorter

distribution half-life of ceftriaxone in goats suggested the rapid distribution of the drug in

body tissue and fluid and that nearly similar to that recorded for ceftriaxone in lactating

goats(012 hour)[9]

for ceftriaxone in lactating ewes (0152 hour)[2]

and for ceftriaxone in

calves( 013hour)[26]

The rapid distribution of ceftriaxone in goats is supported by high rate constant of transfer of

the drug from central to peripheral compartment [K12 = 353 h-1

] as compared to the rate

constant of transfer of the drug from peripheral to central compartment [K21= 295 h-1

] This

value is nearly similar to those reported for cefotaxime in goats (K21=327 h-1

)[38]

On contrast

this value was higher than those recorded for ceftriaxone in lactating goats (K21=143 h-1

)[9]

in

lactating ewes (K21=125 h-1

)[25]

and in domestic cats (K21=154 h-1

)[15]

The apparent volume of distribution of ceftriaxone was (0355plusmn0004LKg) this value is

nearly similar to that recorded for cefaronide in sheep(039 LKg)[7]

cefotaxime in dog (048

lkg)[39]

in goat (051 lkg)

[40] for caphalexin in buffalo calves (041 Lkg)

[41] for cefipime in

ewes and calves (032 lkg) (043Lkg)[29]

and[30]

respectively For ceftriaxone in domestic

cats (057Lkg)[15]

in camel (032Lkg)[42]

On the other hand this result is differ than that

reported for cefotaxime in buffalo calves (117Lkg)[43]

High value of the volume of

distribution suggested extensive penetration power Drug with volume of distribution greater

than one literkilogram indicated wide distribution or extensive tissue binding or both[44]

The

apparent volume of distribution in the present study indicated moderate tissue penetrating

power This result agreed with[15]

for ceftriaxone in domestic cats

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

Ceftriaxone is eliminated in the current study following a single intravenous injection with

elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the

data recorded for ceftizoxime in goats (624hours)[45]

On contrast this value was longer than

that reported for ceftriaxone in lactating ewe (175hours)[25]

for cefaronide in sheep (17

hours)[7]

For cephalexin in buffulo calves (216hours)[41]

for ceftriaxone in healthy horse

(162hours)[46]

also this value is longer than that recorded for ceftriaxone in lactating goats

(144hours)[9]

for cefipime in goats (186hours)[47]

The rate of total body clearance of ceftriaxone following a single intravenous injection is

0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]

On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating

goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)

(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]

respectively

The variation in total body clearance might be attributed to specific interspecies variation

handling of the drug method used healthy status of the animal[48]

The difference between values calculated for pharmacokinetic parameters may be attributed

to animal species the drug formulation employed the age the size or sex o l lf the animal

or even inter individual variation and also due to method of analysis of the drug[49]

Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the

drug reached its peak serum concentrations after one hour of injection with value

of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12

hours post-injection The reported peak serum concentrations neerly similar to that reported

for cephalexin in buffulo calves (457 microgml)[41]

These results is differed than those reported

for ceftriaxone in cross breed calves (188 microgml at 30 min[16]

in Kangro breed of goats

(Capra Hircus) (2640 microgml at 20 min[10][50]

found after intramuscular administration of

ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher

than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]

The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time

(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats

(4932 microgml[47]

The reported maximum serum concentration (Cmax) is higher than that

reported for ceftriaxone in lactating goats(236 microgml)[9]

in lactating ewes (1722 microgml[25]

in

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

goats (2151 microgml)[11]

for cefquinome in camels (123 microgml)[51]

for ceftriaxone in calves

(1534 microgml)[26]

in patanwadi sheep (1553 microgml)[8]

for cefpirome in cattle (101 microgml)[52]

And for ceftiofur in chickens (2594 μgml)[37]

On the other hand the result was lower than

that reported by[6]

who observed the maximum serum concentration (Cmax) of ceftriaxone in

human after ntramuscular administration was (805 microgml) also it was lower than that

reported for ceftriaxone in dog (11510 microgml)[53]

in domestic cats (5440 microgml)[15]

and for

ceftazoxime in goats (8878 microgml)[45]

The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating

ewes by[25]

On contrast it is longer than those reported for ceftriaxone in dogs

(129hours)[53]

for ceftriaxone in lactating goats (07hours)[9]

also the result was longer than

that reported for ceftriaxone in domestic cats (033hours)[15]

in buffulo calves (05 hours)[13]

and for cefpirome in cattle (075hours)[52]

The reported [tmax] is shorter than those reported

for cefquinome in camels (425hours)[51]

in sheep and goats (261 and 262 hours)[36]

and for

ceftiofur in chickens (251 hours)[37]

The elimination half life [t05(β)]

following a single intramuscular administration was 1804 hours This value is nearly agreed

with that recorded for cefquinomein camels (1024hours)[52]

On contrast this result is longer

than that reported for cephalexin in buffalo calves (243hours)[41]

for ceftriaxone in lactating

ewes (177hours)[25]

in buffalo calves (438hours)[13]

in goats (203 hours)[11]

and for

cefipime in goats (165 hours)[47]

The rate of total body clearance of ceftriaxone following a single intramuscular injection is

0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves

(401Lkgh)[13]

in goats (304 Lkgh)[11]

and in sheep (222 Lkgh)[8]

Bioavailability is the fraction of the drug administered by non vascular rout that gains

accesses to the systemic circulation The obtained result revealed that the calculated systemic

bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves

(61)[54]

It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]

On the other

hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]

for ceftriaxone in goats (59)[11]

in calves (47)[55]

On contrast this value is lower than

those reported for cefotaxime in two cats 982 and 93)[57]

for cephradine in goats

wwwwjppscom Vol 5 Issue 01 2016

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

(739)[58]

for ceftazidime in a rabbit (966)[27]

for ceftriaxone in lactating goats (85)[9]

in lactating ewes (836)[25]

in domestic cats 8572[15]

for cefipime in goats 8645[47]

for ceftriaxone in buffulo calves 702[13]

and for ceftiofur in chickens 8890[37]

Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium

infected goats twics dialy for five days revealed that the drug could be detected in a

therapeutic level for 12hours following repeated intramuscular administrations and exceeded

the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]

The relative higher serum concentrations of ceftriaxone after the last dose compared to the

first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12

hours intervals for five consecutive days These observations agreed with data reported by[36]

on comparing the data of serum levels of repeated intramuscular injections with first

intramuscular injection it was revealed that repeated intramuscular injections of cefquinome

have cumulative effect in both species sheep and goats

The obtained result is inconsistent with that reported by[56]

who found thatwhen cefotaxime

was administered repetitively in patients the ratio of maximal serum levels after the last dose

to those after the first dose demonstrated minimal accumulation of intact drug and by[60]

who

found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in

buffalo calves

The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium

infected goats are significantly lower than those in normal goats following repeated

intramuscular injection These lower blood concentrations in Salmonella typhimurium

infected goats might be attributed to the higher penetrating power of ceftriaxone to the

diseased tissues[48]

This phenomenon is similar to data recorded by[61]

who suggested that

Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of

ceftriaxone These alterations might be due to fever and inflammation induced by

infections[59]

proved that the serum concentrations of cephradine following intramuscular

administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after

each intramuscular dose with a lower significant values recorded in Escherichia-coli infected

goats than in normal goatsAlso similer to that reported by[62]

who observed that the

maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep

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1451

Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

in comparison to normal sheepOn contrast[43]

reported that peak plasma level of cefotaxime

in febrile buffalo calves was higher than healthy buffalo calves

In this study the total body clearance (CLtot) in normal goats are significantly lower than in

Salmonella typhimurium infected goats This result supported by[61]

and[63]

fever and

inflammation are cardinal features in bacterial infection which may in turn caused an

increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all

these could lead to increased in the rate at which the drug was delivered to both organs which

were important sites of drug excretion This might somewhat explain the increase in the total

body clearance in infected goats This result is differ than that reported by[64]

who observed

that the clearance of ceftriaxone was significantly reduced in infected mice than in non

infected animals

The highest concentrations of ceftriaxone in milk are recorded 4 hours after each

intramuscular injection with a significant lower value in Salmonella typhimurium infected

goats than in normal goats This might be attributed to accumulation of drug in the inflammed

tissues[48]

This result is similar to those reported by[6559]

who found that milk concentrations

of gentamicin and cephradine were significantly lower in infected goats and cattle than in

normal ones respectively

The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the

non-ionic passive diffusion principle[66]

reported that most drug cross-lipid membranes by

passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly

influenced by the physicochemical properties of the drug[6768]

Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum

ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the

physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]

Milk

contains substantially more lipid and less protein than serum and is slightly more acidic

Therefore drugs which tend to concentrated in milk are weak bases with low serum protein

binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide

and aminothiazole also possesses an hydroxytriazinone group as new and additional

ionization center[70]

these compounds are sufficiently lipid- soluble to be able to penetrate

tissues

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The dose of ceftriaxone used in the present study induced therapeutically concentrations in

milk These concentrations suggested that ceftriaxone would be efficacious in treatment of

mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily

for 3-5 days

The study showed that the urine concentrations of ceftriaxone are greater than the concurrent

serum concentrations following intramuscular injection This observation is similar to those

reported in cows after cephapirin administrations[71]

In the present study urine concentrations of ceftriaxone increased with the repetition of

dosing This observation supported by[72]

after repeated intramuscular administrations of

ceftriaxone in healthy volunteeres

The mean peak urine concentrations of ceftriaxone were reached 2 hours after each

intramuscular injection The lower urine ceftriaxone concentrations in Salmonella

typhimurium infected goats than in normal goats might be attributed to the accumulation of

the drug in the inflamed tissues[48]

The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower

ratio in Salmonella typhimurium infected goats than in normal goats at different time of

sampling This indicates that glomerular filteration seemed to be the main pathway of

ceftriaxone elimination This observation supported by[59]

who found that the ratio between

cephradine clearance from blood of goats to creatinine clearance showed a marked decrease

in Escherichia-coli infected goats than in normal goats This indicated that glomerular

filteration seemed to be the main pathway of cephradine elimination with a limited rate of

tubular reabsorption

CONCLUSION

The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value

referred a better absorption of ceftriaxone from its site of intramuscular administration The

high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular

administrations suggested that ceftriaxone could be used for treatment of mastitis caused by

Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats

The high concentrations of ceftriaxone in urine after repeated intramuscular administrations

suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in

goats

REFERANCES

1 Neu HC Merpol NJ and Fukp (1981) Antibacterial activity of ceftriaxone

abetalactamase stable cephalosporines Antimicrobial agents and chemotherapy 19

414-423

2 Richard DM Heel RC Brogden RN Speight TM Avery GS (1984) Ceftriaxone a

review of its antibacterial activity pharmacological properties and therapeutic uses

Drugs 27 469-527

3 Brogden RN and Ward A (1988) Ceftriaxone a reappraisal of its antibacterial activity

and pharmacokinetic properties and an update on its therapeutic use with particular

reference to once-daily administration Drugs 35 604-645

4 Waxman DJ and Strominger JL (1983) Penicillin-binding proteins and the

mechanism of action of beta-lactam antibiotics Annu Rev Biochem 52(1) 825-869

5 Christ W (1991) properties of cephalosporines Infestion 19 244-252

6 Goonetilleke AK Dev D Aziz I Hughes C Smith MJ Basran GS (1996) A

comparative analysis of pharmacokinetics of ceftriaxone in serum and pleural fluid in

humans a study of once daily administration by intramuscular intravenous routes J

Antimicrob Chemother Dec 38(6) 969-76

7 Guerrini VH Filippich LJ Cao G R English PB Bourne DW (1985)

Pharmacokinetics of cefaronide ceftriaxone and cefperazone in sheep J Vet Pharmacol

Ther 8(2) 120-7

8 Swati Tiwari S Patel UD Bhavsar SK and Thaker AM (2010) Pharmacokinetics

and Bioavailability of Ceftriaxone in Patanwadi Sheep Online veterinary journal 5(2)

9 Ismail MM (2005) Pharmacokinetics urinary and mammary excretion of ceftriaxone in

lactating goats J Vet Med A Physiol Pathol Clin Med Sep 52(7) 354-8

10 Rajinder R prawez S Srivastiva AS (2005) Pharmacokinetics and dosage regimen of

ceftriaxone following its single ntramuscular adminsteration in kagani breed of goats

(Capra Hircus) Journal of reaserch 4(2) 91-93

11 Tiwari S Swati Bhavsar SK Patel UD and Thaker AM (2009) Disposition of

Ceftriaxone in Goats (Capra hircus) Online veterinary journal 4(2)

12 Dardi MS Sharma SK and Srivastava AK (2004) Pharmacokinetics and Dosage

regimen of ceftriaxone in buffalo calves Vet Res Commun 28 331-338

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Assay of samples

According to[20]

three plates were used for each sample Six pores were made three of them

were filled with reference concentration while the other three pores were filled with the

serum milk or urine samples in triplicate manner The plates were incubated at 37degC for 18

hours then the diameter of inhibitory zones were measured The diameter of inhibitory zones

of samples were corrected by using the zone diameter of the reference concentration in the

same manner as previously discussed either by addition or subtraction From the standard

curve the concentrations corresponding to the corrected values of the inhibitory zones were

obtained

Drug clearance

Clearance of the tested drug from the blood of goats was estimated according to the following

equation

Drug clearance10 kg b wt =

Drug concentration in urine (microgml) X rate of diuresis (mlmin) Body weight (Kg)

_________________________________________________________________

Drug concentration in serum (microgml) X 10

Assay of creatinine in serum and urine

Creatinine was assayed by[21]

and performed by kit manufactured by Diamond diagnostics

company

Creatinine clearance

The creatinine clearance (mlmin10 kgbwt) for goats was calculated by the following

equation

Creatinine clearance 10 kgbwt =

Creatinine concentration in urine (mgL) X rate of diuresis (mlmin) Body weight (Kg)

______________________________________________________________________

Creatinine concentration in serum (mgL) X 10

Pharmacokinetic analysis

The pharmacokinetic parameters were calculated by using Winonlin version 12 and other

parameters according to[2223]

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Statistical Analysis

The data were calculated as mean plusmn standard error All statistical analysis were carried out

according to[24]

using the scientific calculator CASIO fx 120

RESULTS

Following a single intravenous injection of 20 mg ceftriaxonekg bwt in normal goats

ceftriaxone could be detected therapeutically for 8 hours post intravenous injection The

serum concentration ndash time curve of ceftriaxone following intravenous injection showed that

the drug obeyed a two compartments open model (Figure 1) The disposition kinetics of

ceftriaxone following a single intravenous intramuscular injection were recorded in table (1)

Intramuscular injection of 20 mg ceftriaxone per kilogram body weight twice daily for five

consecutive days in normal and Salmonella typhimurium infected goats revealed a lower

significant serum ceftriaxone concentration after the first third fifth seventh ninth doses in

Salmonella typhimurium infected goats compared with normal goats The pharmacokinetic

parameters of ceftriaxone after repeated intramuscular injection in normal were compared to

those in Salmonella typhimurium infected goats (Table 2) and (Figure 2 amp 3)

The highest concentrations of ceftriaxone in milk were recorded 4 hours after each

intramuscular dose (Table 3) with a significant lower value in Salmonella typhimurium

infected goats compared with normal goats The calculated milkserum concentrations ratios

of ceftriaxone after repeated intramuscular injection (Table 4)

The amount of urine (mlmin) voided after repeated intramuscular injection of 20 mgkg bwt

Twice daily of ceftriaxone for five consecutive days in normal and experimentally

Salmonella typhimurium infected goats were recorded in table (5) The mean peak urine

concentrations of ceftriaxone (Table 6) were reached 2 hours after each intramuscular dose

with a lower significant concentration in Salmonella typhimurium infected goats compared

with normal goats Urineserum concentration ratios of ceftriaxone after repeated

intramuscular injection in normal and experimentally Salmonella typhimurium infected goats

were calculated and illustrated in table (7) Creatinine clearance (mlmin10 kg bwt)

expressing glomerular filtration rate from blood of goats was shown in table (8) The rate of

ceftriaxone clearance (mlmin10 kg bwt) from blood of goats was shown in table (9) The

ratio between ceftriaxone clearance and creatinine clearance was calculated and illustrated in

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table (10) The data revealed a significant lower ratio in Salmonella typhimurium infected

goats compared with normal goats after the third fifth seventh ninth doses

Table (1) Pharmacokinetics parameters of ceftriaxone (μgml) following a single

intravenous and intramuscuer injection of 20 mgkg bwt in normal goats (n=4)

Intramusculer_

(XplusmnS E)

Intravenous_

(XplusmnS E) Unit Parameters

-------- 1213 plusmn321321 microgml Cdeg

4360plusmn12343 61390 plusmn330 microgml A

43440plusmn43660 636 plusmn43316 h-1

α

43433plusmn3340 43340 plusmn43442 H (α) 43 T

43420plusmn43233 4333plusmn131 h-1

K12

43446plusmn43400 43409plusmn231 h-1

K21

-------- 43440plusmn431 lkg Vdss

4321plusmn6340 43636plusmn1303 microgml B

434446plusmn43419 43443plusmn43136 h-1

β

43141plusmn39340 43411plusmn331 H t05(β))

4344plusmn43401 434440plusmn43409 lkgh Cl tot

-------- 1136plusmn2111300 microgmlh AUMC

-------- 43303 plusmn0314 H MRT

9300plusmn2439 30plusmn034330 microgmlh AUC

3392plusmn63329 -------- F

43436plusmn4361 -------- h-1

K01

43420plusmn3346 -------- h-1

T05(k01)

4342plusmn330 -------- H Tmax(calc))

43021plusmn04343 -------- μgml Cmax(calc)

Cdeg Drug concentration in the serum at zero time immediately after a single intravenous

injection (μgml) A amp B Zero time plasma drug concentration intercepts of biphasic

intravenous disposition curve The coefficient B is based on the terminal exponential phase

(μgml) α amp β Hybrid rate constant of biphasic intravenous disposition curve values of α

and β are related to the slopes of distribution and elimination phase respectively of

biexponential drug disposition curve (h-1

) T05 (α) Distribution half ndash life (h) t05 (β)

Elimination half ndash life (h) K12 First ndash order transfer rate constant for drug distribution from

Central to peripheral compartment (h-1

) K21 First order transfer rate constant for drug

distribution from Peripheral to central compartment (h-1

) Vdss The apparent volume of

distribution which was calculated by steady ndash state method (mlkg) AUMC Area under

moment curve MRT Mean residence time AUC Total area under the serum drug

concentration versus time curve from t = 0 to t = α after administration of a single dose F

Bioavailability Cmax maximum drug concentration Tmax time of maximum observed

concentration in blood

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Figure (1) Arthimatic plot of Serum concentrations of ceftriaxone (μgml) in normal

goats following a single intramuscular injection )diamsdiams( previously given the same doseby

a single intravenous injection () of 20 mg ceftriaxonekgbwt (n=4)

Figure (2) Semilogarthmic graph depicting the time course of ceftriaxone in serum of

normal goats following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt

twice dialy for five consecutive days (n=4)

Figure (3) Semilogarthmic graph depicting the time course of ceftriaxone in serum of

experimentally Salmonella typhimurim infected goats following repeated ntramuscular

injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4) 3

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Table (2) Pharmacokinetic parameters of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected

goats following repeated ntramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)

Dose

Unit

عىهParameters

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1269plusmn0073 7409plusmn121 1352plusmn0132 6373plusmn147 1410plusmn0243 5923plusmn126 1461plusmn0214 5430plusmn125 1424plusmn0172 7635plusmn176 gmlmicro A

0651plusmn0049 plusmn000843116 0720plusmn0008 plusmn00413300 0823plusmn0006 plusmn00263322 0848plusmn0025 plusmn00233323 0786plusmn0028 133plusmn0033 h-1 Α

106plusmn0008 330plusmn0015 0962plusmn0011 0392plusmn0007 0841plusmn0007 0567plusmn012 0818plusmn0024 0569plusmn0012 0885plusmn0030 plusmn00124322 H T05(α)

248plusmn0019 168plusmn0047 203plusmn0075 181plusmn0033 267plusmn0039 120plusmn0028 248plusmn0060 122plusmn0026 222plusmn0100 136plusmn0027 h-1 Kab

0278plusmn0002 0412plusmn0009 0342plusmn0012 0383plusmn0008 0252plusmn0009 0567plusmn0011 0279plusmn0005 00569plusmn0011 0314plusmn0014 0 510plusmn0012 H T05(ab)

0627plusmn0008 0378plusmn0007 0430plusmn0008 0402plusmn0008 0113plusmn00027 0424plusmn0009 0117plusmn0004 0394plusmn0008 0116plusmn0003 0239plusmn0005 h-1 K12

121plusmn0013 0962plusmn0022 141plusmn0021 130plusmn0023 0666plusmn0019 0651plusmn0013 0683plusmn0020 0660plusmn0013 0761plusmn0039 0998plusmn0023 h-1 K21

115plusmn0035 129plusmn0026 104plusmn0047 112plusmn0024 106plusmn0037 122plusmn0025 110plusmn0077 119plusmn0023 0910plusmn0032 123plusmn0023 H Tmax

4182plusmn0628 6108plusmn140 3440plusmn0363 5135plusmn0860 3117plusmn0965 4774plusmn0854 2713plusmn0781 4243plusmn0 870 2479plusmn0547 4065plusmn0825 gmlmicro Cmax

4944plusmn0820 7195plusmn142 4199plusmn0702 6511plusmn130 3190plusmn0688 5117plusmn113 3185plusmn0909 4709plusmn0990 3256plusmn0918 6329plusmn139 gmlmicro B

0164plusmn0003 0189plusmn00043 0181plusmn0002 0178plusmn0004 0181plusmn00035 0167plusmn0004 0214plusmn0009 0195plusmn0005 0249plusmn0918 0272plusmn0006 h-1 β

423plusmn0079 367plusmn0086 381plusmn0047 388plusmn0089 382plusmn0074 415plusmn0081 325plusmn0139 355plusmn0075 277plusmn0056 255plusmn0050 H T05β

0879plusmn0015 0429plusmn0009 109plusmn0004 0426plusmn0009 133plusmn0022 0503plusmn0011 154plusmn0064 0675plusmn0013 171plusmn0060 0693plusmn0014 Lkgh Cltot

28358plusmn215 40775plusmn808 21784plusmn0888 34259plusmn720 17860plusmn155 30705plusmn601 15281plusmn239 24135plusmn555 12175plusmn144 20292plusmn487 gmlhmicro AUC

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (3) Milk concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats

following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)

Dose Time of

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

197plusmn0205 200plusmn0408 125plusmn0104 155plusmn0132 0887plusmn0013 0885plusmn014 0500plusmn0040 074plusmn0012 ------------ ------ Before

200plusmn0408 22plusmn0108 197plusmn0205 200plusmn0408 155plusmn0132 197plusmn0205 100plusmn000 155plusmn0132 ----------- -------- 050

526plusmn0166 700plusmn0408 300plusmn0408 64plusmn0163 25plusmn0204 600plusmn0408 155plusmn0132 582plusmn0118 100plusmn000 520plusmn0166 1

640plusmn0163 900plusmn0408 582plusmn0118 792plusmn0114 582plusmn0118 755plusmn0221 275plusmn0061 700plusmn0408 200plusmn0408 691plusmn0176 2

900plusmn0408 1512plusmn0125 640plusmn0163 1475plusmn0322 640plusmn0163 1400plusmn0408 600plusmn0408 1352plusmn0205 526plusmn166 1225plusmn0595 4

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350plusmn0353 400plusmn0408 300plusmn0408 392plusmn0125 300plusmn0408 35plusmn0353 275plusmn006 300plusmn0408 155plusmn0132 275plusmn0061 6

300 plusmn0408 35plusmn0353 125plusmn0104 200plusmn0408 125plusmn0104 155plusmn01 0825plusmn0062 100plusmn000 0500plusmn0040 0887plusmn0013 8

200plusmn0408 22plusmn0108 100plusmn000 155plusmn0132 100plusmn000 125plusmn0104 0730plusmn002 0825plusmn0078 0422plusmn000 073plusmn0020 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (4) Milkserum concentrations ratios of ceftriaxone in normal and experimentally Salmonella typhimurim infected

goats following repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice daily for five consecutive days (n=4)

Dose Time of

a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

0400plusmn0049 025plusmn0063 0307plusmn0026 021plusmn0019 0365plusmn00064 016plusmn0026 0232plusmn0016 0205plusmn0002 -------- helliphelliphelliphellip Before

0057plusmn0125 0042plusmn00025 0062plusmn00062 0042plusmn0010 0575plusmn00062 0055plusmn0006 0067plusmn0016 0049plusmn0005 --------- -------- 050

0127plusmn00062 0115plusmn00064 008plusmn0012 0117plusmn0004 0088plusmn00054 0122plusmn0008 008plusmn0017 0126plusmn0028 0039plusmn0005 0122plusmn0004 1

018plusmn0008 0185plusmn0010 021plusmn0004 017plusmn0004 0182plusmn0054 0179plusmn0006 0112plusmn00025 0193plusmn0012 0097plusmn0020 019plusmn0004 2

0357plusmn0020 0425plusmn0005 033plusmn0021 045plusmn0009 0285plusmn0082 0494plusmn0015 0395plusmn0016 0572plusmn001 0415plusmn0017 054plusmn0027 4

018plusmn0015 016plusmn0016 0207plusmn0022 0175plusmn0006 0257plusmn0037 0180plusmn0017 0272plusmn0015 0201plusmn003 0196plusmn0016 0222plusmn0002 6

0212plusmn0033 0212plusmn0020 0200plusmn0044 0122plusmn0024 0152plusmn0011 014plusmn0022 0122plusmn00062 0102plusmn0001 0107plusmn00094 0117plusmn0002 8

0372plusmn0042 025plusmn001 0325plusmn0027 0192plusmn0014 0265plusmn00064 0185plusmn0015 0272plusmn0125 0195plusmn0012 0252plusmn0032 0275plusmn0009 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

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Table (5) The amount of urine (mlmin) voided in normal and experimentally Salmonella typhimurim infected goats following

repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)

Dose Time of a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

plusmn00372344 126plusmn0034 130plusmn0030 130plusmn0028 118plusmn0066 118plusmn0067 108plusmn0013 108plusmn0008 ----------- -------- Before

0577plusmn0069 43494057plusmn 045plusmn0060 plusmn0064309 0312plusmn002 033plusmn0012 0340plusmn0024 033plusmn0012 0287plusmn0017 0272plusmn0014 050

0712plusmn0019 0692plusmn0014 068plusmn0081 0697plusmn0006 0672plusmn0011 0675plusmn 0009 0635plusmn0032 0655plusmn0010 0719plusmn0031 0697plusmn0015 1

0837plusmn0025 0787plusmn0021 0732plusmn0011 plusmn00054300 0715plusmn0011 0715plusmn002 0722plusmn0019 0702plusmn0018 0737plusmn0027 0762plusmn0041 2

0535plusmn0095 0507plusmn0021 0447plusmn0022 0452plusmn002 0402plusmn0075 0405plusmn0011 0400plusmn0057 0397plusmn0009 0380plusmn0004 038plusmn001 4

0437plusmn00094 0432plusmn0008 0400plusmn0010 0405plusmn0002 0380plusmn0007 plusmn00044319 0372plusmn0047 037plusmn 0007 0350plusmn0005 0365plusmn0006 6

0397plusmn0028 0410plusmn0008 0380plusmn0012 0395plusmn0009 0355plusmn0086 0352plusmn0007 0340plusmn0004 0345plusmn0005 0302plusmn0004 0335plusmn0005 8

0385plusmn001 0380plusmn0010 0385plusmn00064 0380plusmn0008 0365plusmn0064 0367plusmn0004 0362plusmn0086 0372plusmn0106 0327plusmn0006 0362plusmn0016 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (6) Urine concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats

following repeated intramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)

Dose Time of a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1125plusmn150 1125plusmn15 735plusmn287 81plusmn324 183plusmn03 555plusmn798 37plusmn0811 1815plusmn43290 -------------- ------ Before

2415plusmn357 2625plusmn374 1695plusmn788 249plusmn574 10575plusmn64 2415plusmn357 5400plusmn273 2085plusmn991 102plusmn160 168plusmn547 050

26025plusmn787 2923plusmn479 22425plusmn1225 2805plusmn35 1695plusmn618 2705plusmn471 10200plusmn547 2415plusmn357 6975plusmn225 22425plusmn894 1

29295plusmn765 3012plusmn346 28575plusmn738 2964plusmn415 2355plusmn259 2923plusmn479 1635plusmn561 2645plusmn917 102plusmn547 24825plusmn616 2

23475plusmn430 2482plusmn616 23475plusmn1564 2415plusmn357 1695plusmn788 198plusmn848 8475plusmn309 1515plusmn708 60plusmn212 1185plusmn45 4

1905plusmn45 2355plusmn259 153plusmn519 1935plusmn960 114plusmn948 159plusmn173 6675plusmn309 1215plusmn45 1312plusmn0552 855plusmn193 6

153plusmn1024 1965plusmn135 1335plusmn1229 150plusmn34 735plusmn295 1365plusmn665 6181plusmn339 72plusmn244 907plusmn0951 5025plusmn143 8

135plusmn519 120plusmn346 11725plusmn1551 96plusmn874 525plusmn295 75plusmn173 153plusmn130 39plusmn212 3735plusmn0458 13125plusmn0552 12

Between normal and diseased

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Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (7) Urineserum concentrations ratios of ceftriaxone following repeated ntramuscular injection of 20 mg

ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats

(n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

229plusmn 163 1448plusmn0743 1885plusmn159 1125plusmn0484 533plusmn0260 1050plusmn358 175plusmn0380 4146plusmn116 ------- ------ Before

741plusmn0063 plusmn01553 58plusmn0242 plusmn0149390 422plusmn0206 683plusmn0106 245plusmn0092 667plusmn0306 0510plusmn0081 559plusmn0181 050

651plusmn0243 plusmn0065031 637plusmn0373 plusmn014431 565plusmn0243 plusmn0085300 360plusmn0303 plusmn0110312 279plusmn0121 534plusmn0248 1

836plusmn0150 plusmn00476322 862plusmn0180 plusmn010463 942plusmn0166 plusmn0130631 217plusmn0303 727plusmn0256 508plusmn0186 plusmn01680340 2

939plusmn0235 plusmn01580344 1006plusmn0710 plusmn00750310 999plusmn0542 plusmn02850344 565plusmn0223 641plusmn0241 48plusmn0164 plusmn014834 4

1005plusmn0418 2plusmn018813 1097plusmn0641 plusmn03979300 993plusmn0921 plusmn0252931 619plusmn0483 plusmn0362933 167plusmn0101 642plusmn0644 6

1091plusmn0649 plusmn075332339 1171plusmn0980 995plusmn0415 925plusmn0593 plusmn05593433 886plusmn0408 plusmn02510311 2055plusmn0311 plusmn02046310 8

2392plusmn129 plusmn032731396 1794plusmn0228 1222plusmn124 1418plusmn109 plusmn026733336 580plusmn0397 plusmn03951326 227plusmn0452 plusmn02740316 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (8) Creatinine clearance (mlmin10kgbwt) following repeated intramuscular injection of 20 mg ceftriaxonekgbwt

twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats (n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1115plusmn0703 2265plusmn167 481plusmn0409 672plusmn0817 669plusmn0672 1202plusmn0777 695plusmn0634 1724plusmn179 ----------- ------ Before

0703plusmn0091 147plusmn0305 0718plusmn0141 251plusmn0707 0547plusmn0055 0699plusmn0092 0802plusmn0099 103plusmn0106 295plusmn0124 0458plusmn0037 050

101plusmn0075 161plusmn0093 131plusmn0099 264plusmn0217 161plusmn0146 373plusmn0499 247plusmn0110 4755plusmn0582 214plusmn0234 103plusmn0166 1

157plusmn0198 387plusmn0340 173plusmn0501 267plusmn0217 187plusmn0563 287plusmn0499 451plusmn0223 972plusmn105 263plusmn0399 169plusmn0454 2

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184plusmn0095 346plusmn0444 173plusmn0501 436plusmn0599 383plusmn0299 682plusmn0584 328plusmn0253 119plusmn153 123plusmn0057 292plusmn0742 4

221plusmn0242 411plusmn0661 241plusmn0186 663plusmn0584 308plusmn0234 422plusmn0314 353plusmn0393 548plusmn0901 105plusmn0057 264plusmn0294 6

261plusmn0295 476plusmn0339 319plusmn0273 753plusmn0676 106plusmn0207 0773plusmn0049 228plusmn0175 456plusmn0340 206plusmn0160 404plusmn0419 8

310plusmn0218 409plusmn0434 3264plusmn0153 669plusmn0476 209plusmn0189 235plusmn0337 217plusmn0143 377plusmn0342 240plusmn0218 6055plusmn0176 12

Between normal and diseased

Plt 005 Plt001 Plt0001

Table (9) Ceftriaxone clearance (mlmin10kgbwt following repeated intramuscular injection of 20 mg ceftriaxone kgbwt

twice in normal and experimentally Salmonella typhimurim infected goats (n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1048plusmn121 0557plusmn684 895plusmn113 0547plusmn560 238plusmn0222 103plusmn 480 0668plusmn0157 0173plusmn216 -------- ----------- Before

156plusmn0251 43204plusmn3322 0936plusmn0162 43211plusmn3334 0473plusmn0037 43469plusmn43964 0300plusmn0028 43341plusmn080 0190plusmn0137 43400plusmn43642 050

166plusmn0079 43323plusmn3311 157plusmn0178 43419plusmn3301 137plusmn0115 43311plusmn33022 0883plusmn0054 43341plusmn 133 0616plusmn0153 43120plusmn3301 1

254plusmn0272 43361plusmn3391 222plusmn0093 4331plusmn3390 243plusmn0180 43209plusmn3309 183plusmn0149 43310plusmn2340 128plusmn0153 43312plusmn3390 2

181plusmn0136 43339plusmn3316 161plusmn0129 433plusmn3329 144plusmn0100 43412plusmn3349 0821plusmn0072 0063plusmn0977 0654plusmn0065 43400plusmn4306 4

160plusmn0177 43393plusmn336 152plusmn0200 43416plusmn331 135plusmn0118 4332plusmn3322 0897plusmn0052 43304plusmn3330 0212plusmn0022 43460plusmn43112 6

153plusmn0049 43291plusmn234 163plusmn0242 43346plusmn3300 0891plusmn0272 43306plusmn3310 108plusmn0071 43416plusmn04310 0229plusmn0046 43490plusmn43916 8

340plusmn0522 43214plusmn2341 249plusmn0150 43112plusmn3393 186plusmn0159 43320plusmn336 0773plusmn0094 43390plusmn 134 0264plusmn0043 43400plusmn 54369 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Table (10) Ceftriaxone clearancecreatinine clearance following repeated ntramuscular injection of 20 mg

ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats

(n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

0934plusmn0083 0305plusmn0013 183plusmn0116 0864plusmn0098 0358plusmn0018 0279plusmn0047 0099plusmn0020 0127plusmn0001 ------- ----------- Before

220plusmn0115 0819plusmn0044 131plusmn00414 0458plusmn0029 0876plusmn0063 126plusmn0068 0361plusmn0011 0813plusmn0031 0018plusmn0003 108plusmn0062 050

164plusmn0078 0818plusmn0029 118plusmn0068 0546plusmn0027 0858plusmn0052 0407plusmn0041 0331plusmn0009 0287plusmn0025 0324plusmn0011 0909plusmn0187 1

161plusmn0044 0488plusmn0005 232plusmn128 0329plusmn0027 169plusmn0464 0686plusmn0050 0409plusmn0020 0220plusmn0029 0512plusmn0077 266plusmn177 2

0933plusmn0024 0394plusmn0005 0948plusmn0062 0296plusmn0007 0381plusmn0027 0160plusmn0008 0235plusmn0014 0083plusmn0006 0528plusmn0028 0362plusmn0041 4

0726plusmn0018 0411plusmn0028 0639plusmn0066 0204plusmn0006 0446plusmn0034 0286plusmn0008 0238plusmn0019 0214plusmn0006 020plusmn0013 0382plusmn0028 6

0609plusmn0072 0425plusmn0036 0508plusmn0052 0192plusmn0009 0524plusmn0146 174plusmn0083 0477plusmn0015 0213plusmn00018 0109plusmn0185 0222plusmn0006 8

108plusmn0128 0496plusmn0012 0942plusmn0004 0265plusmn0030 0891plusmn0056 0706plusmn0103 0351plusmn0022 0354plusmn0018 0111plusmn0021 0098plusmn0018 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

DISCUSSION

In the present investigation intravenous injection of 20 mg ceftriaxonekgbwt in normal goats the drug showed high serum level

(92plusmn 0408 μgml) at 5 minutes post-injection then its concentration was decreased gradually till reached its minimum level (18

plusmn0816μgml) at 8hours post-injection

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In the present investigation the intravenous injection of 20 mg ceftriaxonekgbwt In normal

goats showed that the drug disposition best fitted a two-compartments- open model a

compartment of plasma and rapid equilibrating tissues and a deeper slower compartment

The obtained result is consistent with those reported for ceftriaxone in lactating goats[9]

lactating ewe[25]

domestic cat[15]

calves[26]

and patanwadi sheep[8]

Also this phenomenon is

in agreement with those reported for other cephalosporines as ceftazidime in a rabbit[27]

cefepime in dog and neonatal foals[28]

ewes[29]

ceftriaxone in goats[9]

cefipime in calves[30]

ceftiofur in cross-bred friesian cattle[31]

cefipime in calves[32]

ceftiofur in cows[33]

cefpirome

in cross-bred calves[3]

cefazidime in goats[35]

and cefquinome in sheep and goats[36]

cefipime

in chickens[37]

Ceftriaxone was distributed after intravenous injection with a distribution phase (α) equal to

656 per hour with a short distribution half ndash life [t05 (α)] equal to 0104 hour The shorter

distribution half-life of ceftriaxone in goats suggested the rapid distribution of the drug in

body tissue and fluid and that nearly similar to that recorded for ceftriaxone in lactating

goats(012 hour)[9]

for ceftriaxone in lactating ewes (0152 hour)[2]

and for ceftriaxone in

calves( 013hour)[26]

The rapid distribution of ceftriaxone in goats is supported by high rate constant of transfer of

the drug from central to peripheral compartment [K12 = 353 h-1

] as compared to the rate

constant of transfer of the drug from peripheral to central compartment [K21= 295 h-1

] This

value is nearly similar to those reported for cefotaxime in goats (K21=327 h-1

)[38]

On contrast

this value was higher than those recorded for ceftriaxone in lactating goats (K21=143 h-1

)[9]

in

lactating ewes (K21=125 h-1

)[25]

and in domestic cats (K21=154 h-1

)[15]

The apparent volume of distribution of ceftriaxone was (0355plusmn0004LKg) this value is

nearly similar to that recorded for cefaronide in sheep(039 LKg)[7]

cefotaxime in dog (048

lkg)[39]

in goat (051 lkg)

[40] for caphalexin in buffalo calves (041 Lkg)

[41] for cefipime in

ewes and calves (032 lkg) (043Lkg)[29]

and[30]

respectively For ceftriaxone in domestic

cats (057Lkg)[15]

in camel (032Lkg)[42]

On the other hand this result is differ than that

reported for cefotaxime in buffalo calves (117Lkg)[43]

High value of the volume of

distribution suggested extensive penetration power Drug with volume of distribution greater

than one literkilogram indicated wide distribution or extensive tissue binding or both[44]

The

apparent volume of distribution in the present study indicated moderate tissue penetrating

power This result agreed with[15]

for ceftriaxone in domestic cats

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Ceftriaxone is eliminated in the current study following a single intravenous injection with

elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the

data recorded for ceftizoxime in goats (624hours)[45]

On contrast this value was longer than

that reported for ceftriaxone in lactating ewe (175hours)[25]

for cefaronide in sheep (17

hours)[7]

For cephalexin in buffulo calves (216hours)[41]

for ceftriaxone in healthy horse

(162hours)[46]

also this value is longer than that recorded for ceftriaxone in lactating goats

(144hours)[9]

for cefipime in goats (186hours)[47]

The rate of total body clearance of ceftriaxone following a single intravenous injection is

0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]

On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating

goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)

(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]

respectively

The variation in total body clearance might be attributed to specific interspecies variation

handling of the drug method used healthy status of the animal[48]

The difference between values calculated for pharmacokinetic parameters may be attributed

to animal species the drug formulation employed the age the size or sex o l lf the animal

or even inter individual variation and also due to method of analysis of the drug[49]

Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the

drug reached its peak serum concentrations after one hour of injection with value

of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12

hours post-injection The reported peak serum concentrations neerly similar to that reported

for cephalexin in buffulo calves (457 microgml)[41]

These results is differed than those reported

for ceftriaxone in cross breed calves (188 microgml at 30 min[16]

in Kangro breed of goats

(Capra Hircus) (2640 microgml at 20 min[10][50]

found after intramuscular administration of

ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher

than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]

The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time

(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats

(4932 microgml[47]

The reported maximum serum concentration (Cmax) is higher than that

reported for ceftriaxone in lactating goats(236 microgml)[9]

in lactating ewes (1722 microgml[25]

in

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

goats (2151 microgml)[11]

for cefquinome in camels (123 microgml)[51]

for ceftriaxone in calves

(1534 microgml)[26]

in patanwadi sheep (1553 microgml)[8]

for cefpirome in cattle (101 microgml)[52]

And for ceftiofur in chickens (2594 μgml)[37]

On the other hand the result was lower than

that reported by[6]

who observed the maximum serum concentration (Cmax) of ceftriaxone in

human after ntramuscular administration was (805 microgml) also it was lower than that

reported for ceftriaxone in dog (11510 microgml)[53]

in domestic cats (5440 microgml)[15]

and for

ceftazoxime in goats (8878 microgml)[45]

The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating

ewes by[25]

On contrast it is longer than those reported for ceftriaxone in dogs

(129hours)[53]

for ceftriaxone in lactating goats (07hours)[9]

also the result was longer than

that reported for ceftriaxone in domestic cats (033hours)[15]

in buffulo calves (05 hours)[13]

and for cefpirome in cattle (075hours)[52]

The reported [tmax] is shorter than those reported

for cefquinome in camels (425hours)[51]

in sheep and goats (261 and 262 hours)[36]

and for

ceftiofur in chickens (251 hours)[37]

The elimination half life [t05(β)]

following a single intramuscular administration was 1804 hours This value is nearly agreed

with that recorded for cefquinomein camels (1024hours)[52]

On contrast this result is longer

than that reported for cephalexin in buffalo calves (243hours)[41]

for ceftriaxone in lactating

ewes (177hours)[25]

in buffalo calves (438hours)[13]

in goats (203 hours)[11]

and for

cefipime in goats (165 hours)[47]

The rate of total body clearance of ceftriaxone following a single intramuscular injection is

0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves

(401Lkgh)[13]

in goats (304 Lkgh)[11]

and in sheep (222 Lkgh)[8]

Bioavailability is the fraction of the drug administered by non vascular rout that gains

accesses to the systemic circulation The obtained result revealed that the calculated systemic

bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves

(61)[54]

It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]

On the other

hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]

for ceftriaxone in goats (59)[11]

in calves (47)[55]

On contrast this value is lower than

those reported for cefotaxime in two cats 982 and 93)[57]

for cephradine in goats

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

(739)[58]

for ceftazidime in a rabbit (966)[27]

for ceftriaxone in lactating goats (85)[9]

in lactating ewes (836)[25]

in domestic cats 8572[15]

for cefipime in goats 8645[47]

for ceftriaxone in buffulo calves 702[13]

and for ceftiofur in chickens 8890[37]

Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium

infected goats twics dialy for five days revealed that the drug could be detected in a

therapeutic level for 12hours following repeated intramuscular administrations and exceeded

the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]

The relative higher serum concentrations of ceftriaxone after the last dose compared to the

first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12

hours intervals for five consecutive days These observations agreed with data reported by[36]

on comparing the data of serum levels of repeated intramuscular injections with first

intramuscular injection it was revealed that repeated intramuscular injections of cefquinome

have cumulative effect in both species sheep and goats

The obtained result is inconsistent with that reported by[56]

who found thatwhen cefotaxime

was administered repetitively in patients the ratio of maximal serum levels after the last dose

to those after the first dose demonstrated minimal accumulation of intact drug and by[60]

who

found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in

buffalo calves

The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium

infected goats are significantly lower than those in normal goats following repeated

intramuscular injection These lower blood concentrations in Salmonella typhimurium

infected goats might be attributed to the higher penetrating power of ceftriaxone to the

diseased tissues[48]

This phenomenon is similar to data recorded by[61]

who suggested that

Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of

ceftriaxone These alterations might be due to fever and inflammation induced by

infections[59]

proved that the serum concentrations of cephradine following intramuscular

administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after

each intramuscular dose with a lower significant values recorded in Escherichia-coli infected

goats than in normal goatsAlso similer to that reported by[62]

who observed that the

maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

in comparison to normal sheepOn contrast[43]

reported that peak plasma level of cefotaxime

in febrile buffalo calves was higher than healthy buffalo calves

In this study the total body clearance (CLtot) in normal goats are significantly lower than in

Salmonella typhimurium infected goats This result supported by[61]

and[63]

fever and

inflammation are cardinal features in bacterial infection which may in turn caused an

increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all

these could lead to increased in the rate at which the drug was delivered to both organs which

were important sites of drug excretion This might somewhat explain the increase in the total

body clearance in infected goats This result is differ than that reported by[64]

who observed

that the clearance of ceftriaxone was significantly reduced in infected mice than in non

infected animals

The highest concentrations of ceftriaxone in milk are recorded 4 hours after each

intramuscular injection with a significant lower value in Salmonella typhimurium infected

goats than in normal goats This might be attributed to accumulation of drug in the inflammed

tissues[48]

This result is similar to those reported by[6559]

who found that milk concentrations

of gentamicin and cephradine were significantly lower in infected goats and cattle than in

normal ones respectively

The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the

non-ionic passive diffusion principle[66]

reported that most drug cross-lipid membranes by

passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly

influenced by the physicochemical properties of the drug[6768]

Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum

ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the

physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]

Milk

contains substantially more lipid and less protein than serum and is slightly more acidic

Therefore drugs which tend to concentrated in milk are weak bases with low serum protein

binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide

and aminothiazole also possesses an hydroxytriazinone group as new and additional

ionization center[70]

these compounds are sufficiently lipid- soluble to be able to penetrate

tissues

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The dose of ceftriaxone used in the present study induced therapeutically concentrations in

milk These concentrations suggested that ceftriaxone would be efficacious in treatment of

mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily

for 3-5 days

The study showed that the urine concentrations of ceftriaxone are greater than the concurrent

serum concentrations following intramuscular injection This observation is similar to those

reported in cows after cephapirin administrations[71]

In the present study urine concentrations of ceftriaxone increased with the repetition of

dosing This observation supported by[72]

after repeated intramuscular administrations of

ceftriaxone in healthy volunteeres

The mean peak urine concentrations of ceftriaxone were reached 2 hours after each

intramuscular injection The lower urine ceftriaxone concentrations in Salmonella

typhimurium infected goats than in normal goats might be attributed to the accumulation of

the drug in the inflamed tissues[48]

The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower

ratio in Salmonella typhimurium infected goats than in normal goats at different time of

sampling This indicates that glomerular filteration seemed to be the main pathway of

ceftriaxone elimination This observation supported by[59]

who found that the ratio between

cephradine clearance from blood of goats to creatinine clearance showed a marked decrease

in Escherichia-coli infected goats than in normal goats This indicated that glomerular

filteration seemed to be the main pathway of cephradine elimination with a limited rate of

tubular reabsorption

CONCLUSION

The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value

referred a better absorption of ceftriaxone from its site of intramuscular administration The

high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular

administrations suggested that ceftriaxone could be used for treatment of mastitis caused by

Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats

The high concentrations of ceftriaxone in urine after repeated intramuscular administrations

suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in

goats

REFERANCES

1 Neu HC Merpol NJ and Fukp (1981) Antibacterial activity of ceftriaxone

abetalactamase stable cephalosporines Antimicrobial agents and chemotherapy 19

414-423

2 Richard DM Heel RC Brogden RN Speight TM Avery GS (1984) Ceftriaxone a

review of its antibacterial activity pharmacological properties and therapeutic uses

Drugs 27 469-527

3 Brogden RN and Ward A (1988) Ceftriaxone a reappraisal of its antibacterial activity

and pharmacokinetic properties and an update on its therapeutic use with particular

reference to once-daily administration Drugs 35 604-645

4 Waxman DJ and Strominger JL (1983) Penicillin-binding proteins and the

mechanism of action of beta-lactam antibiotics Annu Rev Biochem 52(1) 825-869

5 Christ W (1991) properties of cephalosporines Infestion 19 244-252

6 Goonetilleke AK Dev D Aziz I Hughes C Smith MJ Basran GS (1996) A

comparative analysis of pharmacokinetics of ceftriaxone in serum and pleural fluid in

humans a study of once daily administration by intramuscular intravenous routes J

Antimicrob Chemother Dec 38(6) 969-76

7 Guerrini VH Filippich LJ Cao G R English PB Bourne DW (1985)

Pharmacokinetics of cefaronide ceftriaxone and cefperazone in sheep J Vet Pharmacol

Ther 8(2) 120-7

8 Swati Tiwari S Patel UD Bhavsar SK and Thaker AM (2010) Pharmacokinetics

and Bioavailability of Ceftriaxone in Patanwadi Sheep Online veterinary journal 5(2)

9 Ismail MM (2005) Pharmacokinetics urinary and mammary excretion of ceftriaxone in

lactating goats J Vet Med A Physiol Pathol Clin Med Sep 52(7) 354-8

10 Rajinder R prawez S Srivastiva AS (2005) Pharmacokinetics and dosage regimen of

ceftriaxone following its single ntramuscular adminsteration in kagani breed of goats

(Capra Hircus) Journal of reaserch 4(2) 91-93

11 Tiwari S Swati Bhavsar SK Patel UD and Thaker AM (2009) Disposition of

Ceftriaxone in Goats (Capra hircus) Online veterinary journal 4(2)

12 Dardi MS Sharma SK and Srivastava AK (2004) Pharmacokinetics and Dosage

regimen of ceftriaxone in buffalo calves Vet Res Commun 28 331-338

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Statistical Analysis

The data were calculated as mean plusmn standard error All statistical analysis were carried out

according to[24]

using the scientific calculator CASIO fx 120

RESULTS

Following a single intravenous injection of 20 mg ceftriaxonekg bwt in normal goats

ceftriaxone could be detected therapeutically for 8 hours post intravenous injection The

serum concentration ndash time curve of ceftriaxone following intravenous injection showed that

the drug obeyed a two compartments open model (Figure 1) The disposition kinetics of

ceftriaxone following a single intravenous intramuscular injection were recorded in table (1)

Intramuscular injection of 20 mg ceftriaxone per kilogram body weight twice daily for five

consecutive days in normal and Salmonella typhimurium infected goats revealed a lower

significant serum ceftriaxone concentration after the first third fifth seventh ninth doses in

Salmonella typhimurium infected goats compared with normal goats The pharmacokinetic

parameters of ceftriaxone after repeated intramuscular injection in normal were compared to

those in Salmonella typhimurium infected goats (Table 2) and (Figure 2 amp 3)

The highest concentrations of ceftriaxone in milk were recorded 4 hours after each

intramuscular dose (Table 3) with a significant lower value in Salmonella typhimurium

infected goats compared with normal goats The calculated milkserum concentrations ratios

of ceftriaxone after repeated intramuscular injection (Table 4)

The amount of urine (mlmin) voided after repeated intramuscular injection of 20 mgkg bwt

Twice daily of ceftriaxone for five consecutive days in normal and experimentally

Salmonella typhimurium infected goats were recorded in table (5) The mean peak urine

concentrations of ceftriaxone (Table 6) were reached 2 hours after each intramuscular dose

with a lower significant concentration in Salmonella typhimurium infected goats compared

with normal goats Urineserum concentration ratios of ceftriaxone after repeated

intramuscular injection in normal and experimentally Salmonella typhimurium infected goats

were calculated and illustrated in table (7) Creatinine clearance (mlmin10 kg bwt)

expressing glomerular filtration rate from blood of goats was shown in table (8) The rate of

ceftriaxone clearance (mlmin10 kg bwt) from blood of goats was shown in table (9) The

ratio between ceftriaxone clearance and creatinine clearance was calculated and illustrated in

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

table (10) The data revealed a significant lower ratio in Salmonella typhimurium infected

goats compared with normal goats after the third fifth seventh ninth doses

Table (1) Pharmacokinetics parameters of ceftriaxone (μgml) following a single

intravenous and intramuscuer injection of 20 mgkg bwt in normal goats (n=4)

Intramusculer_

(XplusmnS E)

Intravenous_

(XplusmnS E) Unit Parameters

-------- 1213 plusmn321321 microgml Cdeg

4360plusmn12343 61390 plusmn330 microgml A

43440plusmn43660 636 plusmn43316 h-1

α

43433plusmn3340 43340 plusmn43442 H (α) 43 T

43420plusmn43233 4333plusmn131 h-1

K12

43446plusmn43400 43409plusmn231 h-1

K21

-------- 43440plusmn431 lkg Vdss

4321plusmn6340 43636plusmn1303 microgml B

434446plusmn43419 43443plusmn43136 h-1

β

43141plusmn39340 43411plusmn331 H t05(β))

4344plusmn43401 434440plusmn43409 lkgh Cl tot

-------- 1136plusmn2111300 microgmlh AUMC

-------- 43303 plusmn0314 H MRT

9300plusmn2439 30plusmn034330 microgmlh AUC

3392plusmn63329 -------- F

43436plusmn4361 -------- h-1

K01

43420plusmn3346 -------- h-1

T05(k01)

4342plusmn330 -------- H Tmax(calc))

43021plusmn04343 -------- μgml Cmax(calc)

Cdeg Drug concentration in the serum at zero time immediately after a single intravenous

injection (μgml) A amp B Zero time plasma drug concentration intercepts of biphasic

intravenous disposition curve The coefficient B is based on the terminal exponential phase

(μgml) α amp β Hybrid rate constant of biphasic intravenous disposition curve values of α

and β are related to the slopes of distribution and elimination phase respectively of

biexponential drug disposition curve (h-1

) T05 (α) Distribution half ndash life (h) t05 (β)

Elimination half ndash life (h) K12 First ndash order transfer rate constant for drug distribution from

Central to peripheral compartment (h-1

) K21 First order transfer rate constant for drug

distribution from Peripheral to central compartment (h-1

) Vdss The apparent volume of

distribution which was calculated by steady ndash state method (mlkg) AUMC Area under

moment curve MRT Mean residence time AUC Total area under the serum drug

concentration versus time curve from t = 0 to t = α after administration of a single dose F

Bioavailability Cmax maximum drug concentration Tmax time of maximum observed

concentration in blood

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Figure (1) Arthimatic plot of Serum concentrations of ceftriaxone (μgml) in normal

goats following a single intramuscular injection )diamsdiams( previously given the same doseby

a single intravenous injection () of 20 mg ceftriaxonekgbwt (n=4)

Figure (2) Semilogarthmic graph depicting the time course of ceftriaxone in serum of

normal goats following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt

twice dialy for five consecutive days (n=4)

Figure (3) Semilogarthmic graph depicting the time course of ceftriaxone in serum of

experimentally Salmonella typhimurim infected goats following repeated ntramuscular

injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4) 3

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Table (2) Pharmacokinetic parameters of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected

goats following repeated ntramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)

Dose

Unit

عىهParameters

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1269plusmn0073 7409plusmn121 1352plusmn0132 6373plusmn147 1410plusmn0243 5923plusmn126 1461plusmn0214 5430plusmn125 1424plusmn0172 7635plusmn176 gmlmicro A

0651plusmn0049 plusmn000843116 0720plusmn0008 plusmn00413300 0823plusmn0006 plusmn00263322 0848plusmn0025 plusmn00233323 0786plusmn0028 133plusmn0033 h-1 Α

106plusmn0008 330plusmn0015 0962plusmn0011 0392plusmn0007 0841plusmn0007 0567plusmn012 0818plusmn0024 0569plusmn0012 0885plusmn0030 plusmn00124322 H T05(α)

248plusmn0019 168plusmn0047 203plusmn0075 181plusmn0033 267plusmn0039 120plusmn0028 248plusmn0060 122plusmn0026 222plusmn0100 136plusmn0027 h-1 Kab

0278plusmn0002 0412plusmn0009 0342plusmn0012 0383plusmn0008 0252plusmn0009 0567plusmn0011 0279plusmn0005 00569plusmn0011 0314plusmn0014 0 510plusmn0012 H T05(ab)

0627plusmn0008 0378plusmn0007 0430plusmn0008 0402plusmn0008 0113plusmn00027 0424plusmn0009 0117plusmn0004 0394plusmn0008 0116plusmn0003 0239plusmn0005 h-1 K12

121plusmn0013 0962plusmn0022 141plusmn0021 130plusmn0023 0666plusmn0019 0651plusmn0013 0683plusmn0020 0660plusmn0013 0761plusmn0039 0998plusmn0023 h-1 K21

115plusmn0035 129plusmn0026 104plusmn0047 112plusmn0024 106plusmn0037 122plusmn0025 110plusmn0077 119plusmn0023 0910plusmn0032 123plusmn0023 H Tmax

4182plusmn0628 6108plusmn140 3440plusmn0363 5135plusmn0860 3117plusmn0965 4774plusmn0854 2713plusmn0781 4243plusmn0 870 2479plusmn0547 4065plusmn0825 gmlmicro Cmax

4944plusmn0820 7195plusmn142 4199plusmn0702 6511plusmn130 3190plusmn0688 5117plusmn113 3185plusmn0909 4709plusmn0990 3256plusmn0918 6329plusmn139 gmlmicro B

0164plusmn0003 0189plusmn00043 0181plusmn0002 0178plusmn0004 0181plusmn00035 0167plusmn0004 0214plusmn0009 0195plusmn0005 0249plusmn0918 0272plusmn0006 h-1 β

423plusmn0079 367plusmn0086 381plusmn0047 388plusmn0089 382plusmn0074 415plusmn0081 325plusmn0139 355plusmn0075 277plusmn0056 255plusmn0050 H T05β

0879plusmn0015 0429plusmn0009 109plusmn0004 0426plusmn0009 133plusmn0022 0503plusmn0011 154plusmn0064 0675plusmn0013 171plusmn0060 0693plusmn0014 Lkgh Cltot

28358plusmn215 40775plusmn808 21784plusmn0888 34259plusmn720 17860plusmn155 30705plusmn601 15281plusmn239 24135plusmn555 12175plusmn144 20292plusmn487 gmlhmicro AUC

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (3) Milk concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats

following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)

Dose Time of

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

197plusmn0205 200plusmn0408 125plusmn0104 155plusmn0132 0887plusmn0013 0885plusmn014 0500plusmn0040 074plusmn0012 ------------ ------ Before

200plusmn0408 22plusmn0108 197plusmn0205 200plusmn0408 155plusmn0132 197plusmn0205 100plusmn000 155plusmn0132 ----------- -------- 050

526plusmn0166 700plusmn0408 300plusmn0408 64plusmn0163 25plusmn0204 600plusmn0408 155plusmn0132 582plusmn0118 100plusmn000 520plusmn0166 1

640plusmn0163 900plusmn0408 582plusmn0118 792plusmn0114 582plusmn0118 755plusmn0221 275plusmn0061 700plusmn0408 200plusmn0408 691plusmn0176 2

900plusmn0408 1512plusmn0125 640plusmn0163 1475plusmn0322 640plusmn0163 1400plusmn0408 600plusmn0408 1352plusmn0205 526plusmn166 1225plusmn0595 4

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350plusmn0353 400plusmn0408 300plusmn0408 392plusmn0125 300plusmn0408 35plusmn0353 275plusmn006 300plusmn0408 155plusmn0132 275plusmn0061 6

300 plusmn0408 35plusmn0353 125plusmn0104 200plusmn0408 125plusmn0104 155plusmn01 0825plusmn0062 100plusmn000 0500plusmn0040 0887plusmn0013 8

200plusmn0408 22plusmn0108 100plusmn000 155plusmn0132 100plusmn000 125plusmn0104 0730plusmn002 0825plusmn0078 0422plusmn000 073plusmn0020 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (4) Milkserum concentrations ratios of ceftriaxone in normal and experimentally Salmonella typhimurim infected

goats following repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice daily for five consecutive days (n=4)

Dose Time of

a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

0400plusmn0049 025plusmn0063 0307plusmn0026 021plusmn0019 0365plusmn00064 016plusmn0026 0232plusmn0016 0205plusmn0002 -------- helliphelliphelliphellip Before

0057plusmn0125 0042plusmn00025 0062plusmn00062 0042plusmn0010 0575plusmn00062 0055plusmn0006 0067plusmn0016 0049plusmn0005 --------- -------- 050

0127plusmn00062 0115plusmn00064 008plusmn0012 0117plusmn0004 0088plusmn00054 0122plusmn0008 008plusmn0017 0126plusmn0028 0039plusmn0005 0122plusmn0004 1

018plusmn0008 0185plusmn0010 021plusmn0004 017plusmn0004 0182plusmn0054 0179plusmn0006 0112plusmn00025 0193plusmn0012 0097plusmn0020 019plusmn0004 2

0357plusmn0020 0425plusmn0005 033plusmn0021 045plusmn0009 0285plusmn0082 0494plusmn0015 0395plusmn0016 0572plusmn001 0415plusmn0017 054plusmn0027 4

018plusmn0015 016plusmn0016 0207plusmn0022 0175plusmn0006 0257plusmn0037 0180plusmn0017 0272plusmn0015 0201plusmn003 0196plusmn0016 0222plusmn0002 6

0212plusmn0033 0212plusmn0020 0200plusmn0044 0122plusmn0024 0152plusmn0011 014plusmn0022 0122plusmn00062 0102plusmn0001 0107plusmn00094 0117plusmn0002 8

0372plusmn0042 025plusmn001 0325plusmn0027 0192plusmn0014 0265plusmn00064 0185plusmn0015 0272plusmn0125 0195plusmn0012 0252plusmn0032 0275plusmn0009 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

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Table (5) The amount of urine (mlmin) voided in normal and experimentally Salmonella typhimurim infected goats following

repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)

Dose Time of a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

plusmn00372344 126plusmn0034 130plusmn0030 130plusmn0028 118plusmn0066 118plusmn0067 108plusmn0013 108plusmn0008 ----------- -------- Before

0577plusmn0069 43494057plusmn 045plusmn0060 plusmn0064309 0312plusmn002 033plusmn0012 0340plusmn0024 033plusmn0012 0287plusmn0017 0272plusmn0014 050

0712plusmn0019 0692plusmn0014 068plusmn0081 0697plusmn0006 0672plusmn0011 0675plusmn 0009 0635plusmn0032 0655plusmn0010 0719plusmn0031 0697plusmn0015 1

0837plusmn0025 0787plusmn0021 0732plusmn0011 plusmn00054300 0715plusmn0011 0715plusmn002 0722plusmn0019 0702plusmn0018 0737plusmn0027 0762plusmn0041 2

0535plusmn0095 0507plusmn0021 0447plusmn0022 0452plusmn002 0402plusmn0075 0405plusmn0011 0400plusmn0057 0397plusmn0009 0380plusmn0004 038plusmn001 4

0437plusmn00094 0432plusmn0008 0400plusmn0010 0405plusmn0002 0380plusmn0007 plusmn00044319 0372plusmn0047 037plusmn 0007 0350plusmn0005 0365plusmn0006 6

0397plusmn0028 0410plusmn0008 0380plusmn0012 0395plusmn0009 0355plusmn0086 0352plusmn0007 0340plusmn0004 0345plusmn0005 0302plusmn0004 0335plusmn0005 8

0385plusmn001 0380plusmn0010 0385plusmn00064 0380plusmn0008 0365plusmn0064 0367plusmn0004 0362plusmn0086 0372plusmn0106 0327plusmn0006 0362plusmn0016 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (6) Urine concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats

following repeated intramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)

Dose Time of a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1125plusmn150 1125plusmn15 735plusmn287 81plusmn324 183plusmn03 555plusmn798 37plusmn0811 1815plusmn43290 -------------- ------ Before

2415plusmn357 2625plusmn374 1695plusmn788 249plusmn574 10575plusmn64 2415plusmn357 5400plusmn273 2085plusmn991 102plusmn160 168plusmn547 050

26025plusmn787 2923plusmn479 22425plusmn1225 2805plusmn35 1695plusmn618 2705plusmn471 10200plusmn547 2415plusmn357 6975plusmn225 22425plusmn894 1

29295plusmn765 3012plusmn346 28575plusmn738 2964plusmn415 2355plusmn259 2923plusmn479 1635plusmn561 2645plusmn917 102plusmn547 24825plusmn616 2

23475plusmn430 2482plusmn616 23475plusmn1564 2415plusmn357 1695plusmn788 198plusmn848 8475plusmn309 1515plusmn708 60plusmn212 1185plusmn45 4

1905plusmn45 2355plusmn259 153plusmn519 1935plusmn960 114plusmn948 159plusmn173 6675plusmn309 1215plusmn45 1312plusmn0552 855plusmn193 6

153plusmn1024 1965plusmn135 1335plusmn1229 150plusmn34 735plusmn295 1365plusmn665 6181plusmn339 72plusmn244 907plusmn0951 5025plusmn143 8

135plusmn519 120plusmn346 11725plusmn1551 96plusmn874 525plusmn295 75plusmn173 153plusmn130 39plusmn212 3735plusmn0458 13125plusmn0552 12

Between normal and diseased

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Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (7) Urineserum concentrations ratios of ceftriaxone following repeated ntramuscular injection of 20 mg

ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats

(n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

229plusmn 163 1448plusmn0743 1885plusmn159 1125plusmn0484 533plusmn0260 1050plusmn358 175plusmn0380 4146plusmn116 ------- ------ Before

741plusmn0063 plusmn01553 58plusmn0242 plusmn0149390 422plusmn0206 683plusmn0106 245plusmn0092 667plusmn0306 0510plusmn0081 559plusmn0181 050

651plusmn0243 plusmn0065031 637plusmn0373 plusmn014431 565plusmn0243 plusmn0085300 360plusmn0303 plusmn0110312 279plusmn0121 534plusmn0248 1

836plusmn0150 plusmn00476322 862plusmn0180 plusmn010463 942plusmn0166 plusmn0130631 217plusmn0303 727plusmn0256 508plusmn0186 plusmn01680340 2

939plusmn0235 plusmn01580344 1006plusmn0710 plusmn00750310 999plusmn0542 plusmn02850344 565plusmn0223 641plusmn0241 48plusmn0164 plusmn014834 4

1005plusmn0418 2plusmn018813 1097plusmn0641 plusmn03979300 993plusmn0921 plusmn0252931 619plusmn0483 plusmn0362933 167plusmn0101 642plusmn0644 6

1091plusmn0649 plusmn075332339 1171plusmn0980 995plusmn0415 925plusmn0593 plusmn05593433 886plusmn0408 plusmn02510311 2055plusmn0311 plusmn02046310 8

2392plusmn129 plusmn032731396 1794plusmn0228 1222plusmn124 1418plusmn109 plusmn026733336 580plusmn0397 plusmn03951326 227plusmn0452 plusmn02740316 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (8) Creatinine clearance (mlmin10kgbwt) following repeated intramuscular injection of 20 mg ceftriaxonekgbwt

twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats (n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1115plusmn0703 2265plusmn167 481plusmn0409 672plusmn0817 669plusmn0672 1202plusmn0777 695plusmn0634 1724plusmn179 ----------- ------ Before

0703plusmn0091 147plusmn0305 0718plusmn0141 251plusmn0707 0547plusmn0055 0699plusmn0092 0802plusmn0099 103plusmn0106 295plusmn0124 0458plusmn0037 050

101plusmn0075 161plusmn0093 131plusmn0099 264plusmn0217 161plusmn0146 373plusmn0499 247plusmn0110 4755plusmn0582 214plusmn0234 103plusmn0166 1

157plusmn0198 387plusmn0340 173plusmn0501 267plusmn0217 187plusmn0563 287plusmn0499 451plusmn0223 972plusmn105 263plusmn0399 169plusmn0454 2

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184plusmn0095 346plusmn0444 173plusmn0501 436plusmn0599 383plusmn0299 682plusmn0584 328plusmn0253 119plusmn153 123plusmn0057 292plusmn0742 4

221plusmn0242 411plusmn0661 241plusmn0186 663plusmn0584 308plusmn0234 422plusmn0314 353plusmn0393 548plusmn0901 105plusmn0057 264plusmn0294 6

261plusmn0295 476plusmn0339 319plusmn0273 753plusmn0676 106plusmn0207 0773plusmn0049 228plusmn0175 456plusmn0340 206plusmn0160 404plusmn0419 8

310plusmn0218 409plusmn0434 3264plusmn0153 669plusmn0476 209plusmn0189 235plusmn0337 217plusmn0143 377plusmn0342 240plusmn0218 6055plusmn0176 12

Between normal and diseased

Plt 005 Plt001 Plt0001

Table (9) Ceftriaxone clearance (mlmin10kgbwt following repeated intramuscular injection of 20 mg ceftriaxone kgbwt

twice in normal and experimentally Salmonella typhimurim infected goats (n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1048plusmn121 0557plusmn684 895plusmn113 0547plusmn560 238plusmn0222 103plusmn 480 0668plusmn0157 0173plusmn216 -------- ----------- Before

156plusmn0251 43204plusmn3322 0936plusmn0162 43211plusmn3334 0473plusmn0037 43469plusmn43964 0300plusmn0028 43341plusmn080 0190plusmn0137 43400plusmn43642 050

166plusmn0079 43323plusmn3311 157plusmn0178 43419plusmn3301 137plusmn0115 43311plusmn33022 0883plusmn0054 43341plusmn 133 0616plusmn0153 43120plusmn3301 1

254plusmn0272 43361plusmn3391 222plusmn0093 4331plusmn3390 243plusmn0180 43209plusmn3309 183plusmn0149 43310plusmn2340 128plusmn0153 43312plusmn3390 2

181plusmn0136 43339plusmn3316 161plusmn0129 433plusmn3329 144plusmn0100 43412plusmn3349 0821plusmn0072 0063plusmn0977 0654plusmn0065 43400plusmn4306 4

160plusmn0177 43393plusmn336 152plusmn0200 43416plusmn331 135plusmn0118 4332plusmn3322 0897plusmn0052 43304plusmn3330 0212plusmn0022 43460plusmn43112 6

153plusmn0049 43291plusmn234 163plusmn0242 43346plusmn3300 0891plusmn0272 43306plusmn3310 108plusmn0071 43416plusmn04310 0229plusmn0046 43490plusmn43916 8

340plusmn0522 43214plusmn2341 249plusmn0150 43112plusmn3393 186plusmn0159 43320plusmn336 0773plusmn0094 43390plusmn 134 0264plusmn0043 43400plusmn 54369 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

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Table (10) Ceftriaxone clearancecreatinine clearance following repeated ntramuscular injection of 20 mg

ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats

(n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

0934plusmn0083 0305plusmn0013 183plusmn0116 0864plusmn0098 0358plusmn0018 0279plusmn0047 0099plusmn0020 0127plusmn0001 ------- ----------- Before

220plusmn0115 0819plusmn0044 131plusmn00414 0458plusmn0029 0876plusmn0063 126plusmn0068 0361plusmn0011 0813plusmn0031 0018plusmn0003 108plusmn0062 050

164plusmn0078 0818plusmn0029 118plusmn0068 0546plusmn0027 0858plusmn0052 0407plusmn0041 0331plusmn0009 0287plusmn0025 0324plusmn0011 0909plusmn0187 1

161plusmn0044 0488plusmn0005 232plusmn128 0329plusmn0027 169plusmn0464 0686plusmn0050 0409plusmn0020 0220plusmn0029 0512plusmn0077 266plusmn177 2

0933plusmn0024 0394plusmn0005 0948plusmn0062 0296plusmn0007 0381plusmn0027 0160plusmn0008 0235plusmn0014 0083plusmn0006 0528plusmn0028 0362plusmn0041 4

0726plusmn0018 0411plusmn0028 0639plusmn0066 0204plusmn0006 0446plusmn0034 0286plusmn0008 0238plusmn0019 0214plusmn0006 020plusmn0013 0382plusmn0028 6

0609plusmn0072 0425plusmn0036 0508plusmn0052 0192plusmn0009 0524plusmn0146 174plusmn0083 0477plusmn0015 0213plusmn00018 0109plusmn0185 0222plusmn0006 8

108plusmn0128 0496plusmn0012 0942plusmn0004 0265plusmn0030 0891plusmn0056 0706plusmn0103 0351plusmn0022 0354plusmn0018 0111plusmn0021 0098plusmn0018 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

DISCUSSION

In the present investigation intravenous injection of 20 mg ceftriaxonekgbwt in normal goats the drug showed high serum level

(92plusmn 0408 μgml) at 5 minutes post-injection then its concentration was decreased gradually till reached its minimum level (18

plusmn0816μgml) at 8hours post-injection

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In the present investigation the intravenous injection of 20 mg ceftriaxonekgbwt In normal

goats showed that the drug disposition best fitted a two-compartments- open model a

compartment of plasma and rapid equilibrating tissues and a deeper slower compartment

The obtained result is consistent with those reported for ceftriaxone in lactating goats[9]

lactating ewe[25]

domestic cat[15]

calves[26]

and patanwadi sheep[8]

Also this phenomenon is

in agreement with those reported for other cephalosporines as ceftazidime in a rabbit[27]

cefepime in dog and neonatal foals[28]

ewes[29]

ceftriaxone in goats[9]

cefipime in calves[30]

ceftiofur in cross-bred friesian cattle[31]

cefipime in calves[32]

ceftiofur in cows[33]

cefpirome

in cross-bred calves[3]

cefazidime in goats[35]

and cefquinome in sheep and goats[36]

cefipime

in chickens[37]

Ceftriaxone was distributed after intravenous injection with a distribution phase (α) equal to

656 per hour with a short distribution half ndash life [t05 (α)] equal to 0104 hour The shorter

distribution half-life of ceftriaxone in goats suggested the rapid distribution of the drug in

body tissue and fluid and that nearly similar to that recorded for ceftriaxone in lactating

goats(012 hour)[9]

for ceftriaxone in lactating ewes (0152 hour)[2]

and for ceftriaxone in

calves( 013hour)[26]

The rapid distribution of ceftriaxone in goats is supported by high rate constant of transfer of

the drug from central to peripheral compartment [K12 = 353 h-1

] as compared to the rate

constant of transfer of the drug from peripheral to central compartment [K21= 295 h-1

] This

value is nearly similar to those reported for cefotaxime in goats (K21=327 h-1

)[38]

On contrast

this value was higher than those recorded for ceftriaxone in lactating goats (K21=143 h-1

)[9]

in

lactating ewes (K21=125 h-1

)[25]

and in domestic cats (K21=154 h-1

)[15]

The apparent volume of distribution of ceftriaxone was (0355plusmn0004LKg) this value is

nearly similar to that recorded for cefaronide in sheep(039 LKg)[7]

cefotaxime in dog (048

lkg)[39]

in goat (051 lkg)

[40] for caphalexin in buffalo calves (041 Lkg)

[41] for cefipime in

ewes and calves (032 lkg) (043Lkg)[29]

and[30]

respectively For ceftriaxone in domestic

cats (057Lkg)[15]

in camel (032Lkg)[42]

On the other hand this result is differ than that

reported for cefotaxime in buffalo calves (117Lkg)[43]

High value of the volume of

distribution suggested extensive penetration power Drug with volume of distribution greater

than one literkilogram indicated wide distribution or extensive tissue binding or both[44]

The

apparent volume of distribution in the present study indicated moderate tissue penetrating

power This result agreed with[15]

for ceftriaxone in domestic cats

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Ceftriaxone is eliminated in the current study following a single intravenous injection with

elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the

data recorded for ceftizoxime in goats (624hours)[45]

On contrast this value was longer than

that reported for ceftriaxone in lactating ewe (175hours)[25]

for cefaronide in sheep (17

hours)[7]

For cephalexin in buffulo calves (216hours)[41]

for ceftriaxone in healthy horse

(162hours)[46]

also this value is longer than that recorded for ceftriaxone in lactating goats

(144hours)[9]

for cefipime in goats (186hours)[47]

The rate of total body clearance of ceftriaxone following a single intravenous injection is

0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]

On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating

goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)

(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]

respectively

The variation in total body clearance might be attributed to specific interspecies variation

handling of the drug method used healthy status of the animal[48]

The difference between values calculated for pharmacokinetic parameters may be attributed

to animal species the drug formulation employed the age the size or sex o l lf the animal

or even inter individual variation and also due to method of analysis of the drug[49]

Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the

drug reached its peak serum concentrations after one hour of injection with value

of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12

hours post-injection The reported peak serum concentrations neerly similar to that reported

for cephalexin in buffulo calves (457 microgml)[41]

These results is differed than those reported

for ceftriaxone in cross breed calves (188 microgml at 30 min[16]

in Kangro breed of goats

(Capra Hircus) (2640 microgml at 20 min[10][50]

found after intramuscular administration of

ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher

than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]

The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time

(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats

(4932 microgml[47]

The reported maximum serum concentration (Cmax) is higher than that

reported for ceftriaxone in lactating goats(236 microgml)[9]

in lactating ewes (1722 microgml[25]

in

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

goats (2151 microgml)[11]

for cefquinome in camels (123 microgml)[51]

for ceftriaxone in calves

(1534 microgml)[26]

in patanwadi sheep (1553 microgml)[8]

for cefpirome in cattle (101 microgml)[52]

And for ceftiofur in chickens (2594 μgml)[37]

On the other hand the result was lower than

that reported by[6]

who observed the maximum serum concentration (Cmax) of ceftriaxone in

human after ntramuscular administration was (805 microgml) also it was lower than that

reported for ceftriaxone in dog (11510 microgml)[53]

in domestic cats (5440 microgml)[15]

and for

ceftazoxime in goats (8878 microgml)[45]

The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating

ewes by[25]

On contrast it is longer than those reported for ceftriaxone in dogs

(129hours)[53]

for ceftriaxone in lactating goats (07hours)[9]

also the result was longer than

that reported for ceftriaxone in domestic cats (033hours)[15]

in buffulo calves (05 hours)[13]

and for cefpirome in cattle (075hours)[52]

The reported [tmax] is shorter than those reported

for cefquinome in camels (425hours)[51]

in sheep and goats (261 and 262 hours)[36]

and for

ceftiofur in chickens (251 hours)[37]

The elimination half life [t05(β)]

following a single intramuscular administration was 1804 hours This value is nearly agreed

with that recorded for cefquinomein camels (1024hours)[52]

On contrast this result is longer

than that reported for cephalexin in buffalo calves (243hours)[41]

for ceftriaxone in lactating

ewes (177hours)[25]

in buffalo calves (438hours)[13]

in goats (203 hours)[11]

and for

cefipime in goats (165 hours)[47]

The rate of total body clearance of ceftriaxone following a single intramuscular injection is

0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves

(401Lkgh)[13]

in goats (304 Lkgh)[11]

and in sheep (222 Lkgh)[8]

Bioavailability is the fraction of the drug administered by non vascular rout that gains

accesses to the systemic circulation The obtained result revealed that the calculated systemic

bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves

(61)[54]

It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]

On the other

hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]

for ceftriaxone in goats (59)[11]

in calves (47)[55]

On contrast this value is lower than

those reported for cefotaxime in two cats 982 and 93)[57]

for cephradine in goats

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

(739)[58]

for ceftazidime in a rabbit (966)[27]

for ceftriaxone in lactating goats (85)[9]

in lactating ewes (836)[25]

in domestic cats 8572[15]

for cefipime in goats 8645[47]

for ceftriaxone in buffulo calves 702[13]

and for ceftiofur in chickens 8890[37]

Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium

infected goats twics dialy for five days revealed that the drug could be detected in a

therapeutic level for 12hours following repeated intramuscular administrations and exceeded

the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]

The relative higher serum concentrations of ceftriaxone after the last dose compared to the

first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12

hours intervals for five consecutive days These observations agreed with data reported by[36]

on comparing the data of serum levels of repeated intramuscular injections with first

intramuscular injection it was revealed that repeated intramuscular injections of cefquinome

have cumulative effect in both species sheep and goats

The obtained result is inconsistent with that reported by[56]

who found thatwhen cefotaxime

was administered repetitively in patients the ratio of maximal serum levels after the last dose

to those after the first dose demonstrated minimal accumulation of intact drug and by[60]

who

found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in

buffalo calves

The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium

infected goats are significantly lower than those in normal goats following repeated

intramuscular injection These lower blood concentrations in Salmonella typhimurium

infected goats might be attributed to the higher penetrating power of ceftriaxone to the

diseased tissues[48]

This phenomenon is similar to data recorded by[61]

who suggested that

Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of

ceftriaxone These alterations might be due to fever and inflammation induced by

infections[59]

proved that the serum concentrations of cephradine following intramuscular

administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after

each intramuscular dose with a lower significant values recorded in Escherichia-coli infected

goats than in normal goatsAlso similer to that reported by[62]

who observed that the

maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

in comparison to normal sheepOn contrast[43]

reported that peak plasma level of cefotaxime

in febrile buffalo calves was higher than healthy buffalo calves

In this study the total body clearance (CLtot) in normal goats are significantly lower than in

Salmonella typhimurium infected goats This result supported by[61]

and[63]

fever and

inflammation are cardinal features in bacterial infection which may in turn caused an

increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all

these could lead to increased in the rate at which the drug was delivered to both organs which

were important sites of drug excretion This might somewhat explain the increase in the total

body clearance in infected goats This result is differ than that reported by[64]

who observed

that the clearance of ceftriaxone was significantly reduced in infected mice than in non

infected animals

The highest concentrations of ceftriaxone in milk are recorded 4 hours after each

intramuscular injection with a significant lower value in Salmonella typhimurium infected

goats than in normal goats This might be attributed to accumulation of drug in the inflammed

tissues[48]

This result is similar to those reported by[6559]

who found that milk concentrations

of gentamicin and cephradine were significantly lower in infected goats and cattle than in

normal ones respectively

The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the

non-ionic passive diffusion principle[66]

reported that most drug cross-lipid membranes by

passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly

influenced by the physicochemical properties of the drug[6768]

Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum

ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the

physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]

Milk

contains substantially more lipid and less protein than serum and is slightly more acidic

Therefore drugs which tend to concentrated in milk are weak bases with low serum protein

binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide

and aminothiazole also possesses an hydroxytriazinone group as new and additional

ionization center[70]

these compounds are sufficiently lipid- soluble to be able to penetrate

tissues

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

The dose of ceftriaxone used in the present study induced therapeutically concentrations in

milk These concentrations suggested that ceftriaxone would be efficacious in treatment of

mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily

for 3-5 days

The study showed that the urine concentrations of ceftriaxone are greater than the concurrent

serum concentrations following intramuscular injection This observation is similar to those

reported in cows after cephapirin administrations[71]

In the present study urine concentrations of ceftriaxone increased with the repetition of

dosing This observation supported by[72]

after repeated intramuscular administrations of

ceftriaxone in healthy volunteeres

The mean peak urine concentrations of ceftriaxone were reached 2 hours after each

intramuscular injection The lower urine ceftriaxone concentrations in Salmonella

typhimurium infected goats than in normal goats might be attributed to the accumulation of

the drug in the inflamed tissues[48]

The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower

ratio in Salmonella typhimurium infected goats than in normal goats at different time of

sampling This indicates that glomerular filteration seemed to be the main pathway of

ceftriaxone elimination This observation supported by[59]

who found that the ratio between

cephradine clearance from blood of goats to creatinine clearance showed a marked decrease

in Escherichia-coli infected goats than in normal goats This indicated that glomerular

filteration seemed to be the main pathway of cephradine elimination with a limited rate of

tubular reabsorption

CONCLUSION

The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value

referred a better absorption of ceftriaxone from its site of intramuscular administration The

high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular

administrations suggested that ceftriaxone could be used for treatment of mastitis caused by

Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats

The high concentrations of ceftriaxone in urine after repeated intramuscular administrations

suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in

goats

REFERANCES

1 Neu HC Merpol NJ and Fukp (1981) Antibacterial activity of ceftriaxone

abetalactamase stable cephalosporines Antimicrobial agents and chemotherapy 19

414-423

2 Richard DM Heel RC Brogden RN Speight TM Avery GS (1984) Ceftriaxone a

review of its antibacterial activity pharmacological properties and therapeutic uses

Drugs 27 469-527

3 Brogden RN and Ward A (1988) Ceftriaxone a reappraisal of its antibacterial activity

and pharmacokinetic properties and an update on its therapeutic use with particular

reference to once-daily administration Drugs 35 604-645

4 Waxman DJ and Strominger JL (1983) Penicillin-binding proteins and the

mechanism of action of beta-lactam antibiotics Annu Rev Biochem 52(1) 825-869

5 Christ W (1991) properties of cephalosporines Infestion 19 244-252

6 Goonetilleke AK Dev D Aziz I Hughes C Smith MJ Basran GS (1996) A

comparative analysis of pharmacokinetics of ceftriaxone in serum and pleural fluid in

humans a study of once daily administration by intramuscular intravenous routes J

Antimicrob Chemother Dec 38(6) 969-76

7 Guerrini VH Filippich LJ Cao G R English PB Bourne DW (1985)

Pharmacokinetics of cefaronide ceftriaxone and cefperazone in sheep J Vet Pharmacol

Ther 8(2) 120-7

8 Swati Tiwari S Patel UD Bhavsar SK and Thaker AM (2010) Pharmacokinetics

and Bioavailability of Ceftriaxone in Patanwadi Sheep Online veterinary journal 5(2)

9 Ismail MM (2005) Pharmacokinetics urinary and mammary excretion of ceftriaxone in

lactating goats J Vet Med A Physiol Pathol Clin Med Sep 52(7) 354-8

10 Rajinder R prawez S Srivastiva AS (2005) Pharmacokinetics and dosage regimen of

ceftriaxone following its single ntramuscular adminsteration in kagani breed of goats

(Capra Hircus) Journal of reaserch 4(2) 91-93

11 Tiwari S Swati Bhavsar SK Patel UD and Thaker AM (2009) Disposition of

Ceftriaxone in Goats (Capra hircus) Online veterinary journal 4(2)

12 Dardi MS Sharma SK and Srivastava AK (2004) Pharmacokinetics and Dosage

regimen of ceftriaxone in buffalo calves Vet Res Commun 28 331-338

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

table (10) The data revealed a significant lower ratio in Salmonella typhimurium infected

goats compared with normal goats after the third fifth seventh ninth doses

Table (1) Pharmacokinetics parameters of ceftriaxone (μgml) following a single

intravenous and intramuscuer injection of 20 mgkg bwt in normal goats (n=4)

Intramusculer_

(XplusmnS E)

Intravenous_

(XplusmnS E) Unit Parameters

-------- 1213 plusmn321321 microgml Cdeg

4360plusmn12343 61390 plusmn330 microgml A

43440plusmn43660 636 plusmn43316 h-1

α

43433plusmn3340 43340 plusmn43442 H (α) 43 T

43420plusmn43233 4333plusmn131 h-1

K12

43446plusmn43400 43409plusmn231 h-1

K21

-------- 43440plusmn431 lkg Vdss

4321plusmn6340 43636plusmn1303 microgml B

434446plusmn43419 43443plusmn43136 h-1

β

43141plusmn39340 43411plusmn331 H t05(β))

4344plusmn43401 434440plusmn43409 lkgh Cl tot

-------- 1136plusmn2111300 microgmlh AUMC

-------- 43303 plusmn0314 H MRT

9300plusmn2439 30plusmn034330 microgmlh AUC

3392plusmn63329 -------- F

43436plusmn4361 -------- h-1

K01

43420plusmn3346 -------- h-1

T05(k01)

4342plusmn330 -------- H Tmax(calc))

43021plusmn04343 -------- μgml Cmax(calc)

Cdeg Drug concentration in the serum at zero time immediately after a single intravenous

injection (μgml) A amp B Zero time plasma drug concentration intercepts of biphasic

intravenous disposition curve The coefficient B is based on the terminal exponential phase

(μgml) α amp β Hybrid rate constant of biphasic intravenous disposition curve values of α

and β are related to the slopes of distribution and elimination phase respectively of

biexponential drug disposition curve (h-1

) T05 (α) Distribution half ndash life (h) t05 (β)

Elimination half ndash life (h) K12 First ndash order transfer rate constant for drug distribution from

Central to peripheral compartment (h-1

) K21 First order transfer rate constant for drug

distribution from Peripheral to central compartment (h-1

) Vdss The apparent volume of

distribution which was calculated by steady ndash state method (mlkg) AUMC Area under

moment curve MRT Mean residence time AUC Total area under the serum drug

concentration versus time curve from t = 0 to t = α after administration of a single dose F

Bioavailability Cmax maximum drug concentration Tmax time of maximum observed

concentration in blood

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Figure (1) Arthimatic plot of Serum concentrations of ceftriaxone (μgml) in normal

goats following a single intramuscular injection )diamsdiams( previously given the same doseby

a single intravenous injection () of 20 mg ceftriaxonekgbwt (n=4)

Figure (2) Semilogarthmic graph depicting the time course of ceftriaxone in serum of

normal goats following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt

twice dialy for five consecutive days (n=4)

Figure (3) Semilogarthmic graph depicting the time course of ceftriaxone in serum of

experimentally Salmonella typhimurim infected goats following repeated ntramuscular

injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4) 3

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Table (2) Pharmacokinetic parameters of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected

goats following repeated ntramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)

Dose

Unit

عىهParameters

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1269plusmn0073 7409plusmn121 1352plusmn0132 6373plusmn147 1410plusmn0243 5923plusmn126 1461plusmn0214 5430plusmn125 1424plusmn0172 7635plusmn176 gmlmicro A

0651plusmn0049 plusmn000843116 0720plusmn0008 plusmn00413300 0823plusmn0006 plusmn00263322 0848plusmn0025 plusmn00233323 0786plusmn0028 133plusmn0033 h-1 Α

106plusmn0008 330plusmn0015 0962plusmn0011 0392plusmn0007 0841plusmn0007 0567plusmn012 0818plusmn0024 0569plusmn0012 0885plusmn0030 plusmn00124322 H T05(α)

248plusmn0019 168plusmn0047 203plusmn0075 181plusmn0033 267plusmn0039 120plusmn0028 248plusmn0060 122plusmn0026 222plusmn0100 136plusmn0027 h-1 Kab

0278plusmn0002 0412plusmn0009 0342plusmn0012 0383plusmn0008 0252plusmn0009 0567plusmn0011 0279plusmn0005 00569plusmn0011 0314plusmn0014 0 510plusmn0012 H T05(ab)

0627plusmn0008 0378plusmn0007 0430plusmn0008 0402plusmn0008 0113plusmn00027 0424plusmn0009 0117plusmn0004 0394plusmn0008 0116plusmn0003 0239plusmn0005 h-1 K12

121plusmn0013 0962plusmn0022 141plusmn0021 130plusmn0023 0666plusmn0019 0651plusmn0013 0683plusmn0020 0660plusmn0013 0761plusmn0039 0998plusmn0023 h-1 K21

115plusmn0035 129plusmn0026 104plusmn0047 112plusmn0024 106plusmn0037 122plusmn0025 110plusmn0077 119plusmn0023 0910plusmn0032 123plusmn0023 H Tmax

4182plusmn0628 6108plusmn140 3440plusmn0363 5135plusmn0860 3117plusmn0965 4774plusmn0854 2713plusmn0781 4243plusmn0 870 2479plusmn0547 4065plusmn0825 gmlmicro Cmax

4944plusmn0820 7195plusmn142 4199plusmn0702 6511plusmn130 3190plusmn0688 5117plusmn113 3185plusmn0909 4709plusmn0990 3256plusmn0918 6329plusmn139 gmlmicro B

0164plusmn0003 0189plusmn00043 0181plusmn0002 0178plusmn0004 0181plusmn00035 0167plusmn0004 0214plusmn0009 0195plusmn0005 0249plusmn0918 0272plusmn0006 h-1 β

423plusmn0079 367plusmn0086 381plusmn0047 388plusmn0089 382plusmn0074 415plusmn0081 325plusmn0139 355plusmn0075 277plusmn0056 255plusmn0050 H T05β

0879plusmn0015 0429plusmn0009 109plusmn0004 0426plusmn0009 133plusmn0022 0503plusmn0011 154plusmn0064 0675plusmn0013 171plusmn0060 0693plusmn0014 Lkgh Cltot

28358plusmn215 40775plusmn808 21784plusmn0888 34259plusmn720 17860plusmn155 30705plusmn601 15281plusmn239 24135plusmn555 12175plusmn144 20292plusmn487 gmlhmicro AUC

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (3) Milk concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats

following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)

Dose Time of

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

197plusmn0205 200plusmn0408 125plusmn0104 155plusmn0132 0887plusmn0013 0885plusmn014 0500plusmn0040 074plusmn0012 ------------ ------ Before

200plusmn0408 22plusmn0108 197plusmn0205 200plusmn0408 155plusmn0132 197plusmn0205 100plusmn000 155plusmn0132 ----------- -------- 050

526plusmn0166 700plusmn0408 300plusmn0408 64plusmn0163 25plusmn0204 600plusmn0408 155plusmn0132 582plusmn0118 100plusmn000 520plusmn0166 1

640plusmn0163 900plusmn0408 582plusmn0118 792plusmn0114 582plusmn0118 755plusmn0221 275plusmn0061 700plusmn0408 200plusmn0408 691plusmn0176 2

900plusmn0408 1512plusmn0125 640plusmn0163 1475plusmn0322 640plusmn0163 1400plusmn0408 600plusmn0408 1352plusmn0205 526plusmn166 1225plusmn0595 4

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

350plusmn0353 400plusmn0408 300plusmn0408 392plusmn0125 300plusmn0408 35plusmn0353 275plusmn006 300plusmn0408 155plusmn0132 275plusmn0061 6

300 plusmn0408 35plusmn0353 125plusmn0104 200plusmn0408 125plusmn0104 155plusmn01 0825plusmn0062 100plusmn000 0500plusmn0040 0887plusmn0013 8

200plusmn0408 22plusmn0108 100plusmn000 155plusmn0132 100plusmn000 125plusmn0104 0730plusmn002 0825plusmn0078 0422plusmn000 073plusmn0020 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (4) Milkserum concentrations ratios of ceftriaxone in normal and experimentally Salmonella typhimurim infected

goats following repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice daily for five consecutive days (n=4)

Dose Time of

a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

0400plusmn0049 025plusmn0063 0307plusmn0026 021plusmn0019 0365plusmn00064 016plusmn0026 0232plusmn0016 0205plusmn0002 -------- helliphelliphelliphellip Before

0057plusmn0125 0042plusmn00025 0062plusmn00062 0042plusmn0010 0575plusmn00062 0055plusmn0006 0067plusmn0016 0049plusmn0005 --------- -------- 050

0127plusmn00062 0115plusmn00064 008plusmn0012 0117plusmn0004 0088plusmn00054 0122plusmn0008 008plusmn0017 0126plusmn0028 0039plusmn0005 0122plusmn0004 1

018plusmn0008 0185plusmn0010 021plusmn0004 017plusmn0004 0182plusmn0054 0179plusmn0006 0112plusmn00025 0193plusmn0012 0097plusmn0020 019plusmn0004 2

0357plusmn0020 0425plusmn0005 033plusmn0021 045plusmn0009 0285plusmn0082 0494plusmn0015 0395plusmn0016 0572plusmn001 0415plusmn0017 054plusmn0027 4

018plusmn0015 016plusmn0016 0207plusmn0022 0175plusmn0006 0257plusmn0037 0180plusmn0017 0272plusmn0015 0201plusmn003 0196plusmn0016 0222plusmn0002 6

0212plusmn0033 0212plusmn0020 0200plusmn0044 0122plusmn0024 0152plusmn0011 014plusmn0022 0122plusmn00062 0102plusmn0001 0107plusmn00094 0117plusmn0002 8

0372plusmn0042 025plusmn001 0325plusmn0027 0192plusmn0014 0265plusmn00064 0185plusmn0015 0272plusmn0125 0195plusmn0012 0252plusmn0032 0275plusmn0009 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

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Table (5) The amount of urine (mlmin) voided in normal and experimentally Salmonella typhimurim infected goats following

repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)

Dose Time of a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

plusmn00372344 126plusmn0034 130plusmn0030 130plusmn0028 118plusmn0066 118plusmn0067 108plusmn0013 108plusmn0008 ----------- -------- Before

0577plusmn0069 43494057plusmn 045plusmn0060 plusmn0064309 0312plusmn002 033plusmn0012 0340plusmn0024 033plusmn0012 0287plusmn0017 0272plusmn0014 050

0712plusmn0019 0692plusmn0014 068plusmn0081 0697plusmn0006 0672plusmn0011 0675plusmn 0009 0635plusmn0032 0655plusmn0010 0719plusmn0031 0697plusmn0015 1

0837plusmn0025 0787plusmn0021 0732plusmn0011 plusmn00054300 0715plusmn0011 0715plusmn002 0722plusmn0019 0702plusmn0018 0737plusmn0027 0762plusmn0041 2

0535plusmn0095 0507plusmn0021 0447plusmn0022 0452plusmn002 0402plusmn0075 0405plusmn0011 0400plusmn0057 0397plusmn0009 0380plusmn0004 038plusmn001 4

0437plusmn00094 0432plusmn0008 0400plusmn0010 0405plusmn0002 0380plusmn0007 plusmn00044319 0372plusmn0047 037plusmn 0007 0350plusmn0005 0365plusmn0006 6

0397plusmn0028 0410plusmn0008 0380plusmn0012 0395plusmn0009 0355plusmn0086 0352plusmn0007 0340plusmn0004 0345plusmn0005 0302plusmn0004 0335plusmn0005 8

0385plusmn001 0380plusmn0010 0385plusmn00064 0380plusmn0008 0365plusmn0064 0367plusmn0004 0362plusmn0086 0372plusmn0106 0327plusmn0006 0362plusmn0016 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (6) Urine concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats

following repeated intramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)

Dose Time of a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1125plusmn150 1125plusmn15 735plusmn287 81plusmn324 183plusmn03 555plusmn798 37plusmn0811 1815plusmn43290 -------------- ------ Before

2415plusmn357 2625plusmn374 1695plusmn788 249plusmn574 10575plusmn64 2415plusmn357 5400plusmn273 2085plusmn991 102plusmn160 168plusmn547 050

26025plusmn787 2923plusmn479 22425plusmn1225 2805plusmn35 1695plusmn618 2705plusmn471 10200plusmn547 2415plusmn357 6975plusmn225 22425plusmn894 1

29295plusmn765 3012plusmn346 28575plusmn738 2964plusmn415 2355plusmn259 2923plusmn479 1635plusmn561 2645plusmn917 102plusmn547 24825plusmn616 2

23475plusmn430 2482plusmn616 23475plusmn1564 2415plusmn357 1695plusmn788 198plusmn848 8475plusmn309 1515plusmn708 60plusmn212 1185plusmn45 4

1905plusmn45 2355plusmn259 153plusmn519 1935plusmn960 114plusmn948 159plusmn173 6675plusmn309 1215plusmn45 1312plusmn0552 855plusmn193 6

153plusmn1024 1965plusmn135 1335plusmn1229 150plusmn34 735plusmn295 1365plusmn665 6181plusmn339 72plusmn244 907plusmn0951 5025plusmn143 8

135plusmn519 120plusmn346 11725plusmn1551 96plusmn874 525plusmn295 75plusmn173 153plusmn130 39plusmn212 3735plusmn0458 13125plusmn0552 12

Between normal and diseased

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Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (7) Urineserum concentrations ratios of ceftriaxone following repeated ntramuscular injection of 20 mg

ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats

(n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

229plusmn 163 1448plusmn0743 1885plusmn159 1125plusmn0484 533plusmn0260 1050plusmn358 175plusmn0380 4146plusmn116 ------- ------ Before

741plusmn0063 plusmn01553 58plusmn0242 plusmn0149390 422plusmn0206 683plusmn0106 245plusmn0092 667plusmn0306 0510plusmn0081 559plusmn0181 050

651plusmn0243 plusmn0065031 637plusmn0373 plusmn014431 565plusmn0243 plusmn0085300 360plusmn0303 plusmn0110312 279plusmn0121 534plusmn0248 1

836plusmn0150 plusmn00476322 862plusmn0180 plusmn010463 942plusmn0166 plusmn0130631 217plusmn0303 727plusmn0256 508plusmn0186 plusmn01680340 2

939plusmn0235 plusmn01580344 1006plusmn0710 plusmn00750310 999plusmn0542 plusmn02850344 565plusmn0223 641plusmn0241 48plusmn0164 plusmn014834 4

1005plusmn0418 2plusmn018813 1097plusmn0641 plusmn03979300 993plusmn0921 plusmn0252931 619plusmn0483 plusmn0362933 167plusmn0101 642plusmn0644 6

1091plusmn0649 plusmn075332339 1171plusmn0980 995plusmn0415 925plusmn0593 plusmn05593433 886plusmn0408 plusmn02510311 2055plusmn0311 plusmn02046310 8

2392plusmn129 plusmn032731396 1794plusmn0228 1222plusmn124 1418plusmn109 plusmn026733336 580plusmn0397 plusmn03951326 227plusmn0452 plusmn02740316 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (8) Creatinine clearance (mlmin10kgbwt) following repeated intramuscular injection of 20 mg ceftriaxonekgbwt

twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats (n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1115plusmn0703 2265plusmn167 481plusmn0409 672plusmn0817 669plusmn0672 1202plusmn0777 695plusmn0634 1724plusmn179 ----------- ------ Before

0703plusmn0091 147plusmn0305 0718plusmn0141 251plusmn0707 0547plusmn0055 0699plusmn0092 0802plusmn0099 103plusmn0106 295plusmn0124 0458plusmn0037 050

101plusmn0075 161plusmn0093 131plusmn0099 264plusmn0217 161plusmn0146 373plusmn0499 247plusmn0110 4755plusmn0582 214plusmn0234 103plusmn0166 1

157plusmn0198 387plusmn0340 173plusmn0501 267plusmn0217 187plusmn0563 287plusmn0499 451plusmn0223 972plusmn105 263plusmn0399 169plusmn0454 2

wwwwjppscom Vol 5 Issue 02 2016

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

184plusmn0095 346plusmn0444 173plusmn0501 436plusmn0599 383plusmn0299 682plusmn0584 328plusmn0253 119plusmn153 123plusmn0057 292plusmn0742 4

221plusmn0242 411plusmn0661 241plusmn0186 663plusmn0584 308plusmn0234 422plusmn0314 353plusmn0393 548plusmn0901 105plusmn0057 264plusmn0294 6

261plusmn0295 476plusmn0339 319plusmn0273 753plusmn0676 106plusmn0207 0773plusmn0049 228plusmn0175 456plusmn0340 206plusmn0160 404plusmn0419 8

310plusmn0218 409plusmn0434 3264plusmn0153 669plusmn0476 209plusmn0189 235plusmn0337 217plusmn0143 377plusmn0342 240plusmn0218 6055plusmn0176 12

Between normal and diseased

Plt 005 Plt001 Plt0001

Table (9) Ceftriaxone clearance (mlmin10kgbwt following repeated intramuscular injection of 20 mg ceftriaxone kgbwt

twice in normal and experimentally Salmonella typhimurim infected goats (n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1048plusmn121 0557plusmn684 895plusmn113 0547plusmn560 238plusmn0222 103plusmn 480 0668plusmn0157 0173plusmn216 -------- ----------- Before

156plusmn0251 43204plusmn3322 0936plusmn0162 43211plusmn3334 0473plusmn0037 43469plusmn43964 0300plusmn0028 43341plusmn080 0190plusmn0137 43400plusmn43642 050

166plusmn0079 43323plusmn3311 157plusmn0178 43419plusmn3301 137plusmn0115 43311plusmn33022 0883plusmn0054 43341plusmn 133 0616plusmn0153 43120plusmn3301 1

254plusmn0272 43361plusmn3391 222plusmn0093 4331plusmn3390 243plusmn0180 43209plusmn3309 183plusmn0149 43310plusmn2340 128plusmn0153 43312plusmn3390 2

181plusmn0136 43339plusmn3316 161plusmn0129 433plusmn3329 144plusmn0100 43412plusmn3349 0821plusmn0072 0063plusmn0977 0654plusmn0065 43400plusmn4306 4

160plusmn0177 43393plusmn336 152plusmn0200 43416plusmn331 135plusmn0118 4332plusmn3322 0897plusmn0052 43304plusmn3330 0212plusmn0022 43460plusmn43112 6

153plusmn0049 43291plusmn234 163plusmn0242 43346plusmn3300 0891plusmn0272 43306plusmn3310 108plusmn0071 43416plusmn04310 0229plusmn0046 43490plusmn43916 8

340plusmn0522 43214plusmn2341 249plusmn0150 43112plusmn3393 186plusmn0159 43320plusmn336 0773plusmn0094 43390plusmn 134 0264plusmn0043 43400plusmn 54369 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Table (10) Ceftriaxone clearancecreatinine clearance following repeated ntramuscular injection of 20 mg

ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats

(n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

0934plusmn0083 0305plusmn0013 183plusmn0116 0864plusmn0098 0358plusmn0018 0279plusmn0047 0099plusmn0020 0127plusmn0001 ------- ----------- Before

220plusmn0115 0819plusmn0044 131plusmn00414 0458plusmn0029 0876plusmn0063 126plusmn0068 0361plusmn0011 0813plusmn0031 0018plusmn0003 108plusmn0062 050

164plusmn0078 0818plusmn0029 118plusmn0068 0546plusmn0027 0858plusmn0052 0407plusmn0041 0331plusmn0009 0287plusmn0025 0324plusmn0011 0909plusmn0187 1

161plusmn0044 0488plusmn0005 232plusmn128 0329plusmn0027 169plusmn0464 0686plusmn0050 0409plusmn0020 0220plusmn0029 0512plusmn0077 266plusmn177 2

0933plusmn0024 0394plusmn0005 0948plusmn0062 0296plusmn0007 0381plusmn0027 0160plusmn0008 0235plusmn0014 0083plusmn0006 0528plusmn0028 0362plusmn0041 4

0726plusmn0018 0411plusmn0028 0639plusmn0066 0204plusmn0006 0446plusmn0034 0286plusmn0008 0238plusmn0019 0214plusmn0006 020plusmn0013 0382plusmn0028 6

0609plusmn0072 0425plusmn0036 0508plusmn0052 0192plusmn0009 0524plusmn0146 174plusmn0083 0477plusmn0015 0213plusmn00018 0109plusmn0185 0222plusmn0006 8

108plusmn0128 0496plusmn0012 0942plusmn0004 0265plusmn0030 0891plusmn0056 0706plusmn0103 0351plusmn0022 0354plusmn0018 0111plusmn0021 0098plusmn0018 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

DISCUSSION

In the present investigation intravenous injection of 20 mg ceftriaxonekgbwt in normal goats the drug showed high serum level

(92plusmn 0408 μgml) at 5 minutes post-injection then its concentration was decreased gradually till reached its minimum level (18

plusmn0816μgml) at 8hours post-injection

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

In the present investigation the intravenous injection of 20 mg ceftriaxonekgbwt In normal

goats showed that the drug disposition best fitted a two-compartments- open model a

compartment of plasma and rapid equilibrating tissues and a deeper slower compartment

The obtained result is consistent with those reported for ceftriaxone in lactating goats[9]

lactating ewe[25]

domestic cat[15]

calves[26]

and patanwadi sheep[8]

Also this phenomenon is

in agreement with those reported for other cephalosporines as ceftazidime in a rabbit[27]

cefepime in dog and neonatal foals[28]

ewes[29]

ceftriaxone in goats[9]

cefipime in calves[30]

ceftiofur in cross-bred friesian cattle[31]

cefipime in calves[32]

ceftiofur in cows[33]

cefpirome

in cross-bred calves[3]

cefazidime in goats[35]

and cefquinome in sheep and goats[36]

cefipime

in chickens[37]

Ceftriaxone was distributed after intravenous injection with a distribution phase (α) equal to

656 per hour with a short distribution half ndash life [t05 (α)] equal to 0104 hour The shorter

distribution half-life of ceftriaxone in goats suggested the rapid distribution of the drug in

body tissue and fluid and that nearly similar to that recorded for ceftriaxone in lactating

goats(012 hour)[9]

for ceftriaxone in lactating ewes (0152 hour)[2]

and for ceftriaxone in

calves( 013hour)[26]

The rapid distribution of ceftriaxone in goats is supported by high rate constant of transfer of

the drug from central to peripheral compartment [K12 = 353 h-1

] as compared to the rate

constant of transfer of the drug from peripheral to central compartment [K21= 295 h-1

] This

value is nearly similar to those reported for cefotaxime in goats (K21=327 h-1

)[38]

On contrast

this value was higher than those recorded for ceftriaxone in lactating goats (K21=143 h-1

)[9]

in

lactating ewes (K21=125 h-1

)[25]

and in domestic cats (K21=154 h-1

)[15]

The apparent volume of distribution of ceftriaxone was (0355plusmn0004LKg) this value is

nearly similar to that recorded for cefaronide in sheep(039 LKg)[7]

cefotaxime in dog (048

lkg)[39]

in goat (051 lkg)

[40] for caphalexin in buffalo calves (041 Lkg)

[41] for cefipime in

ewes and calves (032 lkg) (043Lkg)[29]

and[30]

respectively For ceftriaxone in domestic

cats (057Lkg)[15]

in camel (032Lkg)[42]

On the other hand this result is differ than that

reported for cefotaxime in buffalo calves (117Lkg)[43]

High value of the volume of

distribution suggested extensive penetration power Drug with volume of distribution greater

than one literkilogram indicated wide distribution or extensive tissue binding or both[44]

The

apparent volume of distribution in the present study indicated moderate tissue penetrating

power This result agreed with[15]

for ceftriaxone in domestic cats

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

Ceftriaxone is eliminated in the current study following a single intravenous injection with

elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the

data recorded for ceftizoxime in goats (624hours)[45]

On contrast this value was longer than

that reported for ceftriaxone in lactating ewe (175hours)[25]

for cefaronide in sheep (17

hours)[7]

For cephalexin in buffulo calves (216hours)[41]

for ceftriaxone in healthy horse

(162hours)[46]

also this value is longer than that recorded for ceftriaxone in lactating goats

(144hours)[9]

for cefipime in goats (186hours)[47]

The rate of total body clearance of ceftriaxone following a single intravenous injection is

0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]

On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating

goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)

(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]

respectively

The variation in total body clearance might be attributed to specific interspecies variation

handling of the drug method used healthy status of the animal[48]

The difference between values calculated for pharmacokinetic parameters may be attributed

to animal species the drug formulation employed the age the size or sex o l lf the animal

or even inter individual variation and also due to method of analysis of the drug[49]

Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the

drug reached its peak serum concentrations after one hour of injection with value

of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12

hours post-injection The reported peak serum concentrations neerly similar to that reported

for cephalexin in buffulo calves (457 microgml)[41]

These results is differed than those reported

for ceftriaxone in cross breed calves (188 microgml at 30 min[16]

in Kangro breed of goats

(Capra Hircus) (2640 microgml at 20 min[10][50]

found after intramuscular administration of

ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher

than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]

The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time

(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats

(4932 microgml[47]

The reported maximum serum concentration (Cmax) is higher than that

reported for ceftriaxone in lactating goats(236 microgml)[9]

in lactating ewes (1722 microgml[25]

in

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

goats (2151 microgml)[11]

for cefquinome in camels (123 microgml)[51]

for ceftriaxone in calves

(1534 microgml)[26]

in patanwadi sheep (1553 microgml)[8]

for cefpirome in cattle (101 microgml)[52]

And for ceftiofur in chickens (2594 μgml)[37]

On the other hand the result was lower than

that reported by[6]

who observed the maximum serum concentration (Cmax) of ceftriaxone in

human after ntramuscular administration was (805 microgml) also it was lower than that

reported for ceftriaxone in dog (11510 microgml)[53]

in domestic cats (5440 microgml)[15]

and for

ceftazoxime in goats (8878 microgml)[45]

The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating

ewes by[25]

On contrast it is longer than those reported for ceftriaxone in dogs

(129hours)[53]

for ceftriaxone in lactating goats (07hours)[9]

also the result was longer than

that reported for ceftriaxone in domestic cats (033hours)[15]

in buffulo calves (05 hours)[13]

and for cefpirome in cattle (075hours)[52]

The reported [tmax] is shorter than those reported

for cefquinome in camels (425hours)[51]

in sheep and goats (261 and 262 hours)[36]

and for

ceftiofur in chickens (251 hours)[37]

The elimination half life [t05(β)]

following a single intramuscular administration was 1804 hours This value is nearly agreed

with that recorded for cefquinomein camels (1024hours)[52]

On contrast this result is longer

than that reported for cephalexin in buffalo calves (243hours)[41]

for ceftriaxone in lactating

ewes (177hours)[25]

in buffalo calves (438hours)[13]

in goats (203 hours)[11]

and for

cefipime in goats (165 hours)[47]

The rate of total body clearance of ceftriaxone following a single intramuscular injection is

0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves

(401Lkgh)[13]

in goats (304 Lkgh)[11]

and in sheep (222 Lkgh)[8]

Bioavailability is the fraction of the drug administered by non vascular rout that gains

accesses to the systemic circulation The obtained result revealed that the calculated systemic

bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves

(61)[54]

It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]

On the other

hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]

for ceftriaxone in goats (59)[11]

in calves (47)[55]

On contrast this value is lower than

those reported for cefotaxime in two cats 982 and 93)[57]

for cephradine in goats

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

(739)[58]

for ceftazidime in a rabbit (966)[27]

for ceftriaxone in lactating goats (85)[9]

in lactating ewes (836)[25]

in domestic cats 8572[15]

for cefipime in goats 8645[47]

for ceftriaxone in buffulo calves 702[13]

and for ceftiofur in chickens 8890[37]

Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium

infected goats twics dialy for five days revealed that the drug could be detected in a

therapeutic level for 12hours following repeated intramuscular administrations and exceeded

the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]

The relative higher serum concentrations of ceftriaxone after the last dose compared to the

first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12

hours intervals for five consecutive days These observations agreed with data reported by[36]

on comparing the data of serum levels of repeated intramuscular injections with first

intramuscular injection it was revealed that repeated intramuscular injections of cefquinome

have cumulative effect in both species sheep and goats

The obtained result is inconsistent with that reported by[56]

who found thatwhen cefotaxime

was administered repetitively in patients the ratio of maximal serum levels after the last dose

to those after the first dose demonstrated minimal accumulation of intact drug and by[60]

who

found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in

buffalo calves

The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium

infected goats are significantly lower than those in normal goats following repeated

intramuscular injection These lower blood concentrations in Salmonella typhimurium

infected goats might be attributed to the higher penetrating power of ceftriaxone to the

diseased tissues[48]

This phenomenon is similar to data recorded by[61]

who suggested that

Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of

ceftriaxone These alterations might be due to fever and inflammation induced by

infections[59]

proved that the serum concentrations of cephradine following intramuscular

administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after

each intramuscular dose with a lower significant values recorded in Escherichia-coli infected

goats than in normal goatsAlso similer to that reported by[62]

who observed that the

maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

in comparison to normal sheepOn contrast[43]

reported that peak plasma level of cefotaxime

in febrile buffalo calves was higher than healthy buffalo calves

In this study the total body clearance (CLtot) in normal goats are significantly lower than in

Salmonella typhimurium infected goats This result supported by[61]

and[63]

fever and

inflammation are cardinal features in bacterial infection which may in turn caused an

increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all

these could lead to increased in the rate at which the drug was delivered to both organs which

were important sites of drug excretion This might somewhat explain the increase in the total

body clearance in infected goats This result is differ than that reported by[64]

who observed

that the clearance of ceftriaxone was significantly reduced in infected mice than in non

infected animals

The highest concentrations of ceftriaxone in milk are recorded 4 hours after each

intramuscular injection with a significant lower value in Salmonella typhimurium infected

goats than in normal goats This might be attributed to accumulation of drug in the inflammed

tissues[48]

This result is similar to those reported by[6559]

who found that milk concentrations

of gentamicin and cephradine were significantly lower in infected goats and cattle than in

normal ones respectively

The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the

non-ionic passive diffusion principle[66]

reported that most drug cross-lipid membranes by

passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly

influenced by the physicochemical properties of the drug[6768]

Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum

ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the

physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]

Milk

contains substantially more lipid and less protein than serum and is slightly more acidic

Therefore drugs which tend to concentrated in milk are weak bases with low serum protein

binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide

and aminothiazole also possesses an hydroxytriazinone group as new and additional

ionization center[70]

these compounds are sufficiently lipid- soluble to be able to penetrate

tissues

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

The dose of ceftriaxone used in the present study induced therapeutically concentrations in

milk These concentrations suggested that ceftriaxone would be efficacious in treatment of

mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily

for 3-5 days

The study showed that the urine concentrations of ceftriaxone are greater than the concurrent

serum concentrations following intramuscular injection This observation is similar to those

reported in cows after cephapirin administrations[71]

In the present study urine concentrations of ceftriaxone increased with the repetition of

dosing This observation supported by[72]

after repeated intramuscular administrations of

ceftriaxone in healthy volunteeres

The mean peak urine concentrations of ceftriaxone were reached 2 hours after each

intramuscular injection The lower urine ceftriaxone concentrations in Salmonella

typhimurium infected goats than in normal goats might be attributed to the accumulation of

the drug in the inflamed tissues[48]

The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower

ratio in Salmonella typhimurium infected goats than in normal goats at different time of

sampling This indicates that glomerular filteration seemed to be the main pathway of

ceftriaxone elimination This observation supported by[59]

who found that the ratio between

cephradine clearance from blood of goats to creatinine clearance showed a marked decrease

in Escherichia-coli infected goats than in normal goats This indicated that glomerular

filteration seemed to be the main pathway of cephradine elimination with a limited rate of

tubular reabsorption

CONCLUSION

The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value

referred a better absorption of ceftriaxone from its site of intramuscular administration The

high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular

administrations suggested that ceftriaxone could be used for treatment of mastitis caused by

Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats

The high concentrations of ceftriaxone in urine after repeated intramuscular administrations

suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in

goats

REFERANCES

1 Neu HC Merpol NJ and Fukp (1981) Antibacterial activity of ceftriaxone

abetalactamase stable cephalosporines Antimicrobial agents and chemotherapy 19

414-423

2 Richard DM Heel RC Brogden RN Speight TM Avery GS (1984) Ceftriaxone a

review of its antibacterial activity pharmacological properties and therapeutic uses

Drugs 27 469-527

3 Brogden RN and Ward A (1988) Ceftriaxone a reappraisal of its antibacterial activity

and pharmacokinetic properties and an update on its therapeutic use with particular

reference to once-daily administration Drugs 35 604-645

4 Waxman DJ and Strominger JL (1983) Penicillin-binding proteins and the

mechanism of action of beta-lactam antibiotics Annu Rev Biochem 52(1) 825-869

5 Christ W (1991) properties of cephalosporines Infestion 19 244-252

6 Goonetilleke AK Dev D Aziz I Hughes C Smith MJ Basran GS (1996) A

comparative analysis of pharmacokinetics of ceftriaxone in serum and pleural fluid in

humans a study of once daily administration by intramuscular intravenous routes J

Antimicrob Chemother Dec 38(6) 969-76

7 Guerrini VH Filippich LJ Cao G R English PB Bourne DW (1985)

Pharmacokinetics of cefaronide ceftriaxone and cefperazone in sheep J Vet Pharmacol

Ther 8(2) 120-7

8 Swati Tiwari S Patel UD Bhavsar SK and Thaker AM (2010) Pharmacokinetics

and Bioavailability of Ceftriaxone in Patanwadi Sheep Online veterinary journal 5(2)

9 Ismail MM (2005) Pharmacokinetics urinary and mammary excretion of ceftriaxone in

lactating goats J Vet Med A Physiol Pathol Clin Med Sep 52(7) 354-8

10 Rajinder R prawez S Srivastiva AS (2005) Pharmacokinetics and dosage regimen of

ceftriaxone following its single ntramuscular adminsteration in kagani breed of goats

(Capra Hircus) Journal of reaserch 4(2) 91-93

11 Tiwari S Swati Bhavsar SK Patel UD and Thaker AM (2009) Disposition of

Ceftriaxone in Goats (Capra hircus) Online veterinary journal 4(2)

12 Dardi MS Sharma SK and Srivastava AK (2004) Pharmacokinetics and Dosage

regimen of ceftriaxone in buffalo calves Vet Res Commun 28 331-338

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Figure (1) Arthimatic plot of Serum concentrations of ceftriaxone (μgml) in normal

goats following a single intramuscular injection )diamsdiams( previously given the same doseby

a single intravenous injection () of 20 mg ceftriaxonekgbwt (n=4)

Figure (2) Semilogarthmic graph depicting the time course of ceftriaxone in serum of

normal goats following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt

twice dialy for five consecutive days (n=4)

Figure (3) Semilogarthmic graph depicting the time course of ceftriaxone in serum of

experimentally Salmonella typhimurim infected goats following repeated ntramuscular

injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4) 3

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Table (2) Pharmacokinetic parameters of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected

goats following repeated ntramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)

Dose

Unit

عىهParameters

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1269plusmn0073 7409plusmn121 1352plusmn0132 6373plusmn147 1410plusmn0243 5923plusmn126 1461plusmn0214 5430plusmn125 1424plusmn0172 7635plusmn176 gmlmicro A

0651plusmn0049 plusmn000843116 0720plusmn0008 plusmn00413300 0823plusmn0006 plusmn00263322 0848plusmn0025 plusmn00233323 0786plusmn0028 133plusmn0033 h-1 Α

106plusmn0008 330plusmn0015 0962plusmn0011 0392plusmn0007 0841plusmn0007 0567plusmn012 0818plusmn0024 0569plusmn0012 0885plusmn0030 plusmn00124322 H T05(α)

248plusmn0019 168plusmn0047 203plusmn0075 181plusmn0033 267plusmn0039 120plusmn0028 248plusmn0060 122plusmn0026 222plusmn0100 136plusmn0027 h-1 Kab

0278plusmn0002 0412plusmn0009 0342plusmn0012 0383plusmn0008 0252plusmn0009 0567plusmn0011 0279plusmn0005 00569plusmn0011 0314plusmn0014 0 510plusmn0012 H T05(ab)

0627plusmn0008 0378plusmn0007 0430plusmn0008 0402plusmn0008 0113plusmn00027 0424plusmn0009 0117plusmn0004 0394plusmn0008 0116plusmn0003 0239plusmn0005 h-1 K12

121plusmn0013 0962plusmn0022 141plusmn0021 130plusmn0023 0666plusmn0019 0651plusmn0013 0683plusmn0020 0660plusmn0013 0761plusmn0039 0998plusmn0023 h-1 K21

115plusmn0035 129plusmn0026 104plusmn0047 112plusmn0024 106plusmn0037 122plusmn0025 110plusmn0077 119plusmn0023 0910plusmn0032 123plusmn0023 H Tmax

4182plusmn0628 6108plusmn140 3440plusmn0363 5135plusmn0860 3117plusmn0965 4774plusmn0854 2713plusmn0781 4243plusmn0 870 2479plusmn0547 4065plusmn0825 gmlmicro Cmax

4944plusmn0820 7195plusmn142 4199plusmn0702 6511plusmn130 3190plusmn0688 5117plusmn113 3185plusmn0909 4709plusmn0990 3256plusmn0918 6329plusmn139 gmlmicro B

0164plusmn0003 0189plusmn00043 0181plusmn0002 0178plusmn0004 0181plusmn00035 0167plusmn0004 0214plusmn0009 0195plusmn0005 0249plusmn0918 0272plusmn0006 h-1 β

423plusmn0079 367plusmn0086 381plusmn0047 388plusmn0089 382plusmn0074 415plusmn0081 325plusmn0139 355plusmn0075 277plusmn0056 255plusmn0050 H T05β

0879plusmn0015 0429plusmn0009 109plusmn0004 0426plusmn0009 133plusmn0022 0503plusmn0011 154plusmn0064 0675plusmn0013 171plusmn0060 0693plusmn0014 Lkgh Cltot

28358plusmn215 40775plusmn808 21784plusmn0888 34259plusmn720 17860plusmn155 30705plusmn601 15281plusmn239 24135plusmn555 12175plusmn144 20292plusmn487 gmlhmicro AUC

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (3) Milk concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats

following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)

Dose Time of

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

197plusmn0205 200plusmn0408 125plusmn0104 155plusmn0132 0887plusmn0013 0885plusmn014 0500plusmn0040 074plusmn0012 ------------ ------ Before

200plusmn0408 22plusmn0108 197plusmn0205 200plusmn0408 155plusmn0132 197plusmn0205 100plusmn000 155plusmn0132 ----------- -------- 050

526plusmn0166 700plusmn0408 300plusmn0408 64plusmn0163 25plusmn0204 600plusmn0408 155plusmn0132 582plusmn0118 100plusmn000 520plusmn0166 1

640plusmn0163 900plusmn0408 582plusmn0118 792plusmn0114 582plusmn0118 755plusmn0221 275plusmn0061 700plusmn0408 200plusmn0408 691plusmn0176 2

900plusmn0408 1512plusmn0125 640plusmn0163 1475plusmn0322 640plusmn0163 1400plusmn0408 600plusmn0408 1352plusmn0205 526plusmn166 1225plusmn0595 4

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350plusmn0353 400plusmn0408 300plusmn0408 392plusmn0125 300plusmn0408 35plusmn0353 275plusmn006 300plusmn0408 155plusmn0132 275plusmn0061 6

300 plusmn0408 35plusmn0353 125plusmn0104 200plusmn0408 125plusmn0104 155plusmn01 0825plusmn0062 100plusmn000 0500plusmn0040 0887plusmn0013 8

200plusmn0408 22plusmn0108 100plusmn000 155plusmn0132 100plusmn000 125plusmn0104 0730plusmn002 0825plusmn0078 0422plusmn000 073plusmn0020 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (4) Milkserum concentrations ratios of ceftriaxone in normal and experimentally Salmonella typhimurim infected

goats following repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice daily for five consecutive days (n=4)

Dose Time of

a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

0400plusmn0049 025plusmn0063 0307plusmn0026 021plusmn0019 0365plusmn00064 016plusmn0026 0232plusmn0016 0205plusmn0002 -------- helliphelliphelliphellip Before

0057plusmn0125 0042plusmn00025 0062plusmn00062 0042plusmn0010 0575plusmn00062 0055plusmn0006 0067plusmn0016 0049plusmn0005 --------- -------- 050

0127plusmn00062 0115plusmn00064 008plusmn0012 0117plusmn0004 0088plusmn00054 0122plusmn0008 008plusmn0017 0126plusmn0028 0039plusmn0005 0122plusmn0004 1

018plusmn0008 0185plusmn0010 021plusmn0004 017plusmn0004 0182plusmn0054 0179plusmn0006 0112plusmn00025 0193plusmn0012 0097plusmn0020 019plusmn0004 2

0357plusmn0020 0425plusmn0005 033plusmn0021 045plusmn0009 0285plusmn0082 0494plusmn0015 0395plusmn0016 0572plusmn001 0415plusmn0017 054plusmn0027 4

018plusmn0015 016plusmn0016 0207plusmn0022 0175plusmn0006 0257plusmn0037 0180plusmn0017 0272plusmn0015 0201plusmn003 0196plusmn0016 0222plusmn0002 6

0212plusmn0033 0212plusmn0020 0200plusmn0044 0122plusmn0024 0152plusmn0011 014plusmn0022 0122plusmn00062 0102plusmn0001 0107plusmn00094 0117plusmn0002 8

0372plusmn0042 025plusmn001 0325plusmn0027 0192plusmn0014 0265plusmn00064 0185plusmn0015 0272plusmn0125 0195plusmn0012 0252plusmn0032 0275plusmn0009 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

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Table (5) The amount of urine (mlmin) voided in normal and experimentally Salmonella typhimurim infected goats following

repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)

Dose Time of a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

plusmn00372344 126plusmn0034 130plusmn0030 130plusmn0028 118plusmn0066 118plusmn0067 108plusmn0013 108plusmn0008 ----------- -------- Before

0577plusmn0069 43494057plusmn 045plusmn0060 plusmn0064309 0312plusmn002 033plusmn0012 0340plusmn0024 033plusmn0012 0287plusmn0017 0272plusmn0014 050

0712plusmn0019 0692plusmn0014 068plusmn0081 0697plusmn0006 0672plusmn0011 0675plusmn 0009 0635plusmn0032 0655plusmn0010 0719plusmn0031 0697plusmn0015 1

0837plusmn0025 0787plusmn0021 0732plusmn0011 plusmn00054300 0715plusmn0011 0715plusmn002 0722plusmn0019 0702plusmn0018 0737plusmn0027 0762plusmn0041 2

0535plusmn0095 0507plusmn0021 0447plusmn0022 0452plusmn002 0402plusmn0075 0405plusmn0011 0400plusmn0057 0397plusmn0009 0380plusmn0004 038plusmn001 4

0437plusmn00094 0432plusmn0008 0400plusmn0010 0405plusmn0002 0380plusmn0007 plusmn00044319 0372plusmn0047 037plusmn 0007 0350plusmn0005 0365plusmn0006 6

0397plusmn0028 0410plusmn0008 0380plusmn0012 0395plusmn0009 0355plusmn0086 0352plusmn0007 0340plusmn0004 0345plusmn0005 0302plusmn0004 0335plusmn0005 8

0385plusmn001 0380plusmn0010 0385plusmn00064 0380plusmn0008 0365plusmn0064 0367plusmn0004 0362plusmn0086 0372plusmn0106 0327plusmn0006 0362plusmn0016 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (6) Urine concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats

following repeated intramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)

Dose Time of a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1125plusmn150 1125plusmn15 735plusmn287 81plusmn324 183plusmn03 555plusmn798 37plusmn0811 1815plusmn43290 -------------- ------ Before

2415plusmn357 2625plusmn374 1695plusmn788 249plusmn574 10575plusmn64 2415plusmn357 5400plusmn273 2085plusmn991 102plusmn160 168plusmn547 050

26025plusmn787 2923plusmn479 22425plusmn1225 2805plusmn35 1695plusmn618 2705plusmn471 10200plusmn547 2415plusmn357 6975plusmn225 22425plusmn894 1

29295plusmn765 3012plusmn346 28575plusmn738 2964plusmn415 2355plusmn259 2923plusmn479 1635plusmn561 2645plusmn917 102plusmn547 24825plusmn616 2

23475plusmn430 2482plusmn616 23475plusmn1564 2415plusmn357 1695plusmn788 198plusmn848 8475plusmn309 1515plusmn708 60plusmn212 1185plusmn45 4

1905plusmn45 2355plusmn259 153plusmn519 1935plusmn960 114plusmn948 159plusmn173 6675plusmn309 1215plusmn45 1312plusmn0552 855plusmn193 6

153plusmn1024 1965plusmn135 1335plusmn1229 150plusmn34 735plusmn295 1365plusmn665 6181plusmn339 72plusmn244 907plusmn0951 5025plusmn143 8

135plusmn519 120plusmn346 11725plusmn1551 96plusmn874 525plusmn295 75plusmn173 153plusmn130 39plusmn212 3735plusmn0458 13125plusmn0552 12

Between normal and diseased

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Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (7) Urineserum concentrations ratios of ceftriaxone following repeated ntramuscular injection of 20 mg

ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats

(n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

229plusmn 163 1448plusmn0743 1885plusmn159 1125plusmn0484 533plusmn0260 1050plusmn358 175plusmn0380 4146plusmn116 ------- ------ Before

741plusmn0063 plusmn01553 58plusmn0242 plusmn0149390 422plusmn0206 683plusmn0106 245plusmn0092 667plusmn0306 0510plusmn0081 559plusmn0181 050

651plusmn0243 plusmn0065031 637plusmn0373 plusmn014431 565plusmn0243 plusmn0085300 360plusmn0303 plusmn0110312 279plusmn0121 534plusmn0248 1

836plusmn0150 plusmn00476322 862plusmn0180 plusmn010463 942plusmn0166 plusmn0130631 217plusmn0303 727plusmn0256 508plusmn0186 plusmn01680340 2

939plusmn0235 plusmn01580344 1006plusmn0710 plusmn00750310 999plusmn0542 plusmn02850344 565plusmn0223 641plusmn0241 48plusmn0164 plusmn014834 4

1005plusmn0418 2plusmn018813 1097plusmn0641 plusmn03979300 993plusmn0921 plusmn0252931 619plusmn0483 plusmn0362933 167plusmn0101 642plusmn0644 6

1091plusmn0649 plusmn075332339 1171plusmn0980 995plusmn0415 925plusmn0593 plusmn05593433 886plusmn0408 plusmn02510311 2055plusmn0311 plusmn02046310 8

2392plusmn129 plusmn032731396 1794plusmn0228 1222plusmn124 1418plusmn109 plusmn026733336 580plusmn0397 plusmn03951326 227plusmn0452 plusmn02740316 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (8) Creatinine clearance (mlmin10kgbwt) following repeated intramuscular injection of 20 mg ceftriaxonekgbwt

twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats (n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1115plusmn0703 2265plusmn167 481plusmn0409 672plusmn0817 669plusmn0672 1202plusmn0777 695plusmn0634 1724plusmn179 ----------- ------ Before

0703plusmn0091 147plusmn0305 0718plusmn0141 251plusmn0707 0547plusmn0055 0699plusmn0092 0802plusmn0099 103plusmn0106 295plusmn0124 0458plusmn0037 050

101plusmn0075 161plusmn0093 131plusmn0099 264plusmn0217 161plusmn0146 373plusmn0499 247plusmn0110 4755plusmn0582 214plusmn0234 103plusmn0166 1

157plusmn0198 387plusmn0340 173plusmn0501 267plusmn0217 187plusmn0563 287plusmn0499 451plusmn0223 972plusmn105 263plusmn0399 169plusmn0454 2

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184plusmn0095 346plusmn0444 173plusmn0501 436plusmn0599 383plusmn0299 682plusmn0584 328plusmn0253 119plusmn153 123plusmn0057 292plusmn0742 4

221plusmn0242 411plusmn0661 241plusmn0186 663plusmn0584 308plusmn0234 422plusmn0314 353plusmn0393 548plusmn0901 105plusmn0057 264plusmn0294 6

261plusmn0295 476plusmn0339 319plusmn0273 753plusmn0676 106plusmn0207 0773plusmn0049 228plusmn0175 456plusmn0340 206plusmn0160 404plusmn0419 8

310plusmn0218 409plusmn0434 3264plusmn0153 669plusmn0476 209plusmn0189 235plusmn0337 217plusmn0143 377plusmn0342 240plusmn0218 6055plusmn0176 12

Between normal and diseased

Plt 005 Plt001 Plt0001

Table (9) Ceftriaxone clearance (mlmin10kgbwt following repeated intramuscular injection of 20 mg ceftriaxone kgbwt

twice in normal and experimentally Salmonella typhimurim infected goats (n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1048plusmn121 0557plusmn684 895plusmn113 0547plusmn560 238plusmn0222 103plusmn 480 0668plusmn0157 0173plusmn216 -------- ----------- Before

156plusmn0251 43204plusmn3322 0936plusmn0162 43211plusmn3334 0473plusmn0037 43469plusmn43964 0300plusmn0028 43341plusmn080 0190plusmn0137 43400plusmn43642 050

166plusmn0079 43323plusmn3311 157plusmn0178 43419plusmn3301 137plusmn0115 43311plusmn33022 0883plusmn0054 43341plusmn 133 0616plusmn0153 43120plusmn3301 1

254plusmn0272 43361plusmn3391 222plusmn0093 4331plusmn3390 243plusmn0180 43209plusmn3309 183plusmn0149 43310plusmn2340 128plusmn0153 43312plusmn3390 2

181plusmn0136 43339plusmn3316 161plusmn0129 433plusmn3329 144plusmn0100 43412plusmn3349 0821plusmn0072 0063plusmn0977 0654plusmn0065 43400plusmn4306 4

160plusmn0177 43393plusmn336 152plusmn0200 43416plusmn331 135plusmn0118 4332plusmn3322 0897plusmn0052 43304plusmn3330 0212plusmn0022 43460plusmn43112 6

153plusmn0049 43291plusmn234 163plusmn0242 43346plusmn3300 0891plusmn0272 43306plusmn3310 108plusmn0071 43416plusmn04310 0229plusmn0046 43490plusmn43916 8

340plusmn0522 43214plusmn2341 249plusmn0150 43112plusmn3393 186plusmn0159 43320plusmn336 0773plusmn0094 43390plusmn 134 0264plusmn0043 43400plusmn 54369 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

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Table (10) Ceftriaxone clearancecreatinine clearance following repeated ntramuscular injection of 20 mg

ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats

(n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

0934plusmn0083 0305plusmn0013 183plusmn0116 0864plusmn0098 0358plusmn0018 0279plusmn0047 0099plusmn0020 0127plusmn0001 ------- ----------- Before

220plusmn0115 0819plusmn0044 131plusmn00414 0458plusmn0029 0876plusmn0063 126plusmn0068 0361plusmn0011 0813plusmn0031 0018plusmn0003 108plusmn0062 050

164plusmn0078 0818plusmn0029 118plusmn0068 0546plusmn0027 0858plusmn0052 0407plusmn0041 0331plusmn0009 0287plusmn0025 0324plusmn0011 0909plusmn0187 1

161plusmn0044 0488plusmn0005 232plusmn128 0329plusmn0027 169plusmn0464 0686plusmn0050 0409plusmn0020 0220plusmn0029 0512plusmn0077 266plusmn177 2

0933plusmn0024 0394plusmn0005 0948plusmn0062 0296plusmn0007 0381plusmn0027 0160plusmn0008 0235plusmn0014 0083plusmn0006 0528plusmn0028 0362plusmn0041 4

0726plusmn0018 0411plusmn0028 0639plusmn0066 0204plusmn0006 0446plusmn0034 0286plusmn0008 0238plusmn0019 0214plusmn0006 020plusmn0013 0382plusmn0028 6

0609plusmn0072 0425plusmn0036 0508plusmn0052 0192plusmn0009 0524plusmn0146 174plusmn0083 0477plusmn0015 0213plusmn00018 0109plusmn0185 0222plusmn0006 8

108plusmn0128 0496plusmn0012 0942plusmn0004 0265plusmn0030 0891plusmn0056 0706plusmn0103 0351plusmn0022 0354plusmn0018 0111plusmn0021 0098plusmn0018 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

DISCUSSION

In the present investigation intravenous injection of 20 mg ceftriaxonekgbwt in normal goats the drug showed high serum level

(92plusmn 0408 μgml) at 5 minutes post-injection then its concentration was decreased gradually till reached its minimum level (18

plusmn0816μgml) at 8hours post-injection

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In the present investigation the intravenous injection of 20 mg ceftriaxonekgbwt In normal

goats showed that the drug disposition best fitted a two-compartments- open model a

compartment of plasma and rapid equilibrating tissues and a deeper slower compartment

The obtained result is consistent with those reported for ceftriaxone in lactating goats[9]

lactating ewe[25]

domestic cat[15]

calves[26]

and patanwadi sheep[8]

Also this phenomenon is

in agreement with those reported for other cephalosporines as ceftazidime in a rabbit[27]

cefepime in dog and neonatal foals[28]

ewes[29]

ceftriaxone in goats[9]

cefipime in calves[30]

ceftiofur in cross-bred friesian cattle[31]

cefipime in calves[32]

ceftiofur in cows[33]

cefpirome

in cross-bred calves[3]

cefazidime in goats[35]

and cefquinome in sheep and goats[36]

cefipime

in chickens[37]

Ceftriaxone was distributed after intravenous injection with a distribution phase (α) equal to

656 per hour with a short distribution half ndash life [t05 (α)] equal to 0104 hour The shorter

distribution half-life of ceftriaxone in goats suggested the rapid distribution of the drug in

body tissue and fluid and that nearly similar to that recorded for ceftriaxone in lactating

goats(012 hour)[9]

for ceftriaxone in lactating ewes (0152 hour)[2]

and for ceftriaxone in

calves( 013hour)[26]

The rapid distribution of ceftriaxone in goats is supported by high rate constant of transfer of

the drug from central to peripheral compartment [K12 = 353 h-1

] as compared to the rate

constant of transfer of the drug from peripheral to central compartment [K21= 295 h-1

] This

value is nearly similar to those reported for cefotaxime in goats (K21=327 h-1

)[38]

On contrast

this value was higher than those recorded for ceftriaxone in lactating goats (K21=143 h-1

)[9]

in

lactating ewes (K21=125 h-1

)[25]

and in domestic cats (K21=154 h-1

)[15]

The apparent volume of distribution of ceftriaxone was (0355plusmn0004LKg) this value is

nearly similar to that recorded for cefaronide in sheep(039 LKg)[7]

cefotaxime in dog (048

lkg)[39]

in goat (051 lkg)

[40] for caphalexin in buffalo calves (041 Lkg)

[41] for cefipime in

ewes and calves (032 lkg) (043Lkg)[29]

and[30]

respectively For ceftriaxone in domestic

cats (057Lkg)[15]

in camel (032Lkg)[42]

On the other hand this result is differ than that

reported for cefotaxime in buffalo calves (117Lkg)[43]

High value of the volume of

distribution suggested extensive penetration power Drug with volume of distribution greater

than one literkilogram indicated wide distribution or extensive tissue binding or both[44]

The

apparent volume of distribution in the present study indicated moderate tissue penetrating

power This result agreed with[15]

for ceftriaxone in domestic cats

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Ceftriaxone is eliminated in the current study following a single intravenous injection with

elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the

data recorded for ceftizoxime in goats (624hours)[45]

On contrast this value was longer than

that reported for ceftriaxone in lactating ewe (175hours)[25]

for cefaronide in sheep (17

hours)[7]

For cephalexin in buffulo calves (216hours)[41]

for ceftriaxone in healthy horse

(162hours)[46]

also this value is longer than that recorded for ceftriaxone in lactating goats

(144hours)[9]

for cefipime in goats (186hours)[47]

The rate of total body clearance of ceftriaxone following a single intravenous injection is

0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]

On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating

goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)

(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]

respectively

The variation in total body clearance might be attributed to specific interspecies variation

handling of the drug method used healthy status of the animal[48]

The difference between values calculated for pharmacokinetic parameters may be attributed

to animal species the drug formulation employed the age the size or sex o l lf the animal

or even inter individual variation and also due to method of analysis of the drug[49]

Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the

drug reached its peak serum concentrations after one hour of injection with value

of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12

hours post-injection The reported peak serum concentrations neerly similar to that reported

for cephalexin in buffulo calves (457 microgml)[41]

These results is differed than those reported

for ceftriaxone in cross breed calves (188 microgml at 30 min[16]

in Kangro breed of goats

(Capra Hircus) (2640 microgml at 20 min[10][50]

found after intramuscular administration of

ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher

than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]

The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time

(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats

(4932 microgml[47]

The reported maximum serum concentration (Cmax) is higher than that

reported for ceftriaxone in lactating goats(236 microgml)[9]

in lactating ewes (1722 microgml[25]

in

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

goats (2151 microgml)[11]

for cefquinome in camels (123 microgml)[51]

for ceftriaxone in calves

(1534 microgml)[26]

in patanwadi sheep (1553 microgml)[8]

for cefpirome in cattle (101 microgml)[52]

And for ceftiofur in chickens (2594 μgml)[37]

On the other hand the result was lower than

that reported by[6]

who observed the maximum serum concentration (Cmax) of ceftriaxone in

human after ntramuscular administration was (805 microgml) also it was lower than that

reported for ceftriaxone in dog (11510 microgml)[53]

in domestic cats (5440 microgml)[15]

and for

ceftazoxime in goats (8878 microgml)[45]

The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating

ewes by[25]

On contrast it is longer than those reported for ceftriaxone in dogs

(129hours)[53]

for ceftriaxone in lactating goats (07hours)[9]

also the result was longer than

that reported for ceftriaxone in domestic cats (033hours)[15]

in buffulo calves (05 hours)[13]

and for cefpirome in cattle (075hours)[52]

The reported [tmax] is shorter than those reported

for cefquinome in camels (425hours)[51]

in sheep and goats (261 and 262 hours)[36]

and for

ceftiofur in chickens (251 hours)[37]

The elimination half life [t05(β)]

following a single intramuscular administration was 1804 hours This value is nearly agreed

with that recorded for cefquinomein camels (1024hours)[52]

On contrast this result is longer

than that reported for cephalexin in buffalo calves (243hours)[41]

for ceftriaxone in lactating

ewes (177hours)[25]

in buffalo calves (438hours)[13]

in goats (203 hours)[11]

and for

cefipime in goats (165 hours)[47]

The rate of total body clearance of ceftriaxone following a single intramuscular injection is

0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves

(401Lkgh)[13]

in goats (304 Lkgh)[11]

and in sheep (222 Lkgh)[8]

Bioavailability is the fraction of the drug administered by non vascular rout that gains

accesses to the systemic circulation The obtained result revealed that the calculated systemic

bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves

(61)[54]

It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]

On the other

hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]

for ceftriaxone in goats (59)[11]

in calves (47)[55]

On contrast this value is lower than

those reported for cefotaxime in two cats 982 and 93)[57]

for cephradine in goats

wwwwjppscom Vol 5 Issue 01 2016

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

(739)[58]

for ceftazidime in a rabbit (966)[27]

for ceftriaxone in lactating goats (85)[9]

in lactating ewes (836)[25]

in domestic cats 8572[15]

for cefipime in goats 8645[47]

for ceftriaxone in buffulo calves 702[13]

and for ceftiofur in chickens 8890[37]

Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium

infected goats twics dialy for five days revealed that the drug could be detected in a

therapeutic level for 12hours following repeated intramuscular administrations and exceeded

the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]

The relative higher serum concentrations of ceftriaxone after the last dose compared to the

first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12

hours intervals for five consecutive days These observations agreed with data reported by[36]

on comparing the data of serum levels of repeated intramuscular injections with first

intramuscular injection it was revealed that repeated intramuscular injections of cefquinome

have cumulative effect in both species sheep and goats

The obtained result is inconsistent with that reported by[56]

who found thatwhen cefotaxime

was administered repetitively in patients the ratio of maximal serum levels after the last dose

to those after the first dose demonstrated minimal accumulation of intact drug and by[60]

who

found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in

buffalo calves

The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium

infected goats are significantly lower than those in normal goats following repeated

intramuscular injection These lower blood concentrations in Salmonella typhimurium

infected goats might be attributed to the higher penetrating power of ceftriaxone to the

diseased tissues[48]

This phenomenon is similar to data recorded by[61]

who suggested that

Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of

ceftriaxone These alterations might be due to fever and inflammation induced by

infections[59]

proved that the serum concentrations of cephradine following intramuscular

administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after

each intramuscular dose with a lower significant values recorded in Escherichia-coli infected

goats than in normal goatsAlso similer to that reported by[62]

who observed that the

maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

in comparison to normal sheepOn contrast[43]

reported that peak plasma level of cefotaxime

in febrile buffalo calves was higher than healthy buffalo calves

In this study the total body clearance (CLtot) in normal goats are significantly lower than in

Salmonella typhimurium infected goats This result supported by[61]

and[63]

fever and

inflammation are cardinal features in bacterial infection which may in turn caused an

increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all

these could lead to increased in the rate at which the drug was delivered to both organs which

were important sites of drug excretion This might somewhat explain the increase in the total

body clearance in infected goats This result is differ than that reported by[64]

who observed

that the clearance of ceftriaxone was significantly reduced in infected mice than in non

infected animals

The highest concentrations of ceftriaxone in milk are recorded 4 hours after each

intramuscular injection with a significant lower value in Salmonella typhimurium infected

goats than in normal goats This might be attributed to accumulation of drug in the inflammed

tissues[48]

This result is similar to those reported by[6559]

who found that milk concentrations

of gentamicin and cephradine were significantly lower in infected goats and cattle than in

normal ones respectively

The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the

non-ionic passive diffusion principle[66]

reported that most drug cross-lipid membranes by

passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly

influenced by the physicochemical properties of the drug[6768]

Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum

ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the

physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]

Milk

contains substantially more lipid and less protein than serum and is slightly more acidic

Therefore drugs which tend to concentrated in milk are weak bases with low serum protein

binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide

and aminothiazole also possesses an hydroxytriazinone group as new and additional

ionization center[70]

these compounds are sufficiently lipid- soluble to be able to penetrate

tissues

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

The dose of ceftriaxone used in the present study induced therapeutically concentrations in

milk These concentrations suggested that ceftriaxone would be efficacious in treatment of

mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily

for 3-5 days

The study showed that the urine concentrations of ceftriaxone are greater than the concurrent

serum concentrations following intramuscular injection This observation is similar to those

reported in cows after cephapirin administrations[71]

In the present study urine concentrations of ceftriaxone increased with the repetition of

dosing This observation supported by[72]

after repeated intramuscular administrations of

ceftriaxone in healthy volunteeres

The mean peak urine concentrations of ceftriaxone were reached 2 hours after each

intramuscular injection The lower urine ceftriaxone concentrations in Salmonella

typhimurium infected goats than in normal goats might be attributed to the accumulation of

the drug in the inflamed tissues[48]

The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower

ratio in Salmonella typhimurium infected goats than in normal goats at different time of

sampling This indicates that glomerular filteration seemed to be the main pathway of

ceftriaxone elimination This observation supported by[59]

who found that the ratio between

cephradine clearance from blood of goats to creatinine clearance showed a marked decrease

in Escherichia-coli infected goats than in normal goats This indicated that glomerular

filteration seemed to be the main pathway of cephradine elimination with a limited rate of

tubular reabsorption

CONCLUSION

The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value

referred a better absorption of ceftriaxone from its site of intramuscular administration The

high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular

administrations suggested that ceftriaxone could be used for treatment of mastitis caused by

Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats

The high concentrations of ceftriaxone in urine after repeated intramuscular administrations

suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in

goats

REFERANCES

1 Neu HC Merpol NJ and Fukp (1981) Antibacterial activity of ceftriaxone

abetalactamase stable cephalosporines Antimicrobial agents and chemotherapy 19

414-423

2 Richard DM Heel RC Brogden RN Speight TM Avery GS (1984) Ceftriaxone a

review of its antibacterial activity pharmacological properties and therapeutic uses

Drugs 27 469-527

3 Brogden RN and Ward A (1988) Ceftriaxone a reappraisal of its antibacterial activity

and pharmacokinetic properties and an update on its therapeutic use with particular

reference to once-daily administration Drugs 35 604-645

4 Waxman DJ and Strominger JL (1983) Penicillin-binding proteins and the

mechanism of action of beta-lactam antibiotics Annu Rev Biochem 52(1) 825-869

5 Christ W (1991) properties of cephalosporines Infestion 19 244-252

6 Goonetilleke AK Dev D Aziz I Hughes C Smith MJ Basran GS (1996) A

comparative analysis of pharmacokinetics of ceftriaxone in serum and pleural fluid in

humans a study of once daily administration by intramuscular intravenous routes J

Antimicrob Chemother Dec 38(6) 969-76

7 Guerrini VH Filippich LJ Cao G R English PB Bourne DW (1985)

Pharmacokinetics of cefaronide ceftriaxone and cefperazone in sheep J Vet Pharmacol

Ther 8(2) 120-7

8 Swati Tiwari S Patel UD Bhavsar SK and Thaker AM (2010) Pharmacokinetics

and Bioavailability of Ceftriaxone in Patanwadi Sheep Online veterinary journal 5(2)

9 Ismail MM (2005) Pharmacokinetics urinary and mammary excretion of ceftriaxone in

lactating goats J Vet Med A Physiol Pathol Clin Med Sep 52(7) 354-8

10 Rajinder R prawez S Srivastiva AS (2005) Pharmacokinetics and dosage regimen of

ceftriaxone following its single ntramuscular adminsteration in kagani breed of goats

(Capra Hircus) Journal of reaserch 4(2) 91-93

11 Tiwari S Swati Bhavsar SK Patel UD and Thaker AM (2009) Disposition of

Ceftriaxone in Goats (Capra hircus) Online veterinary journal 4(2)

12 Dardi MS Sharma SK and Srivastava AK (2004) Pharmacokinetics and Dosage

regimen of ceftriaxone in buffalo calves Vet Res Commun 28 331-338

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Table (2) Pharmacokinetic parameters of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected

goats following repeated ntramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)

Dose

Unit

عىهParameters

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1269plusmn0073 7409plusmn121 1352plusmn0132 6373plusmn147 1410plusmn0243 5923plusmn126 1461plusmn0214 5430plusmn125 1424plusmn0172 7635plusmn176 gmlmicro A

0651plusmn0049 plusmn000843116 0720plusmn0008 plusmn00413300 0823plusmn0006 plusmn00263322 0848plusmn0025 plusmn00233323 0786plusmn0028 133plusmn0033 h-1 Α

106plusmn0008 330plusmn0015 0962plusmn0011 0392plusmn0007 0841plusmn0007 0567plusmn012 0818plusmn0024 0569plusmn0012 0885plusmn0030 plusmn00124322 H T05(α)

248plusmn0019 168plusmn0047 203plusmn0075 181plusmn0033 267plusmn0039 120plusmn0028 248plusmn0060 122plusmn0026 222plusmn0100 136plusmn0027 h-1 Kab

0278plusmn0002 0412plusmn0009 0342plusmn0012 0383plusmn0008 0252plusmn0009 0567plusmn0011 0279plusmn0005 00569plusmn0011 0314plusmn0014 0 510plusmn0012 H T05(ab)

0627plusmn0008 0378plusmn0007 0430plusmn0008 0402plusmn0008 0113plusmn00027 0424plusmn0009 0117plusmn0004 0394plusmn0008 0116plusmn0003 0239plusmn0005 h-1 K12

121plusmn0013 0962plusmn0022 141plusmn0021 130plusmn0023 0666plusmn0019 0651plusmn0013 0683plusmn0020 0660plusmn0013 0761plusmn0039 0998plusmn0023 h-1 K21

115plusmn0035 129plusmn0026 104plusmn0047 112plusmn0024 106plusmn0037 122plusmn0025 110plusmn0077 119plusmn0023 0910plusmn0032 123plusmn0023 H Tmax

4182plusmn0628 6108plusmn140 3440plusmn0363 5135plusmn0860 3117plusmn0965 4774plusmn0854 2713plusmn0781 4243plusmn0 870 2479plusmn0547 4065plusmn0825 gmlmicro Cmax

4944plusmn0820 7195plusmn142 4199plusmn0702 6511plusmn130 3190plusmn0688 5117plusmn113 3185plusmn0909 4709plusmn0990 3256plusmn0918 6329plusmn139 gmlmicro B

0164plusmn0003 0189plusmn00043 0181plusmn0002 0178plusmn0004 0181plusmn00035 0167plusmn0004 0214plusmn0009 0195plusmn0005 0249plusmn0918 0272plusmn0006 h-1 β

423plusmn0079 367plusmn0086 381plusmn0047 388plusmn0089 382plusmn0074 415plusmn0081 325plusmn0139 355plusmn0075 277plusmn0056 255plusmn0050 H T05β

0879plusmn0015 0429plusmn0009 109plusmn0004 0426plusmn0009 133plusmn0022 0503plusmn0011 154plusmn0064 0675plusmn0013 171plusmn0060 0693plusmn0014 Lkgh Cltot

28358plusmn215 40775plusmn808 21784plusmn0888 34259plusmn720 17860plusmn155 30705plusmn601 15281plusmn239 24135plusmn555 12175plusmn144 20292plusmn487 gmlhmicro AUC

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (3) Milk concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats

following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)

Dose Time of

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

197plusmn0205 200plusmn0408 125plusmn0104 155plusmn0132 0887plusmn0013 0885plusmn014 0500plusmn0040 074plusmn0012 ------------ ------ Before

200plusmn0408 22plusmn0108 197plusmn0205 200plusmn0408 155plusmn0132 197plusmn0205 100plusmn000 155plusmn0132 ----------- -------- 050

526plusmn0166 700plusmn0408 300plusmn0408 64plusmn0163 25plusmn0204 600plusmn0408 155plusmn0132 582plusmn0118 100plusmn000 520plusmn0166 1

640plusmn0163 900plusmn0408 582plusmn0118 792plusmn0114 582plusmn0118 755plusmn0221 275plusmn0061 700plusmn0408 200plusmn0408 691plusmn0176 2

900plusmn0408 1512plusmn0125 640plusmn0163 1475plusmn0322 640plusmn0163 1400plusmn0408 600plusmn0408 1352plusmn0205 526plusmn166 1225plusmn0595 4

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

350plusmn0353 400plusmn0408 300plusmn0408 392plusmn0125 300plusmn0408 35plusmn0353 275plusmn006 300plusmn0408 155plusmn0132 275plusmn0061 6

300 plusmn0408 35plusmn0353 125plusmn0104 200plusmn0408 125plusmn0104 155plusmn01 0825plusmn0062 100plusmn000 0500plusmn0040 0887plusmn0013 8

200plusmn0408 22plusmn0108 100plusmn000 155plusmn0132 100plusmn000 125plusmn0104 0730plusmn002 0825plusmn0078 0422plusmn000 073plusmn0020 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (4) Milkserum concentrations ratios of ceftriaxone in normal and experimentally Salmonella typhimurim infected

goats following repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice daily for five consecutive days (n=4)

Dose Time of

a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

0400plusmn0049 025plusmn0063 0307plusmn0026 021plusmn0019 0365plusmn00064 016plusmn0026 0232plusmn0016 0205plusmn0002 -------- helliphelliphelliphellip Before

0057plusmn0125 0042plusmn00025 0062plusmn00062 0042plusmn0010 0575plusmn00062 0055plusmn0006 0067plusmn0016 0049plusmn0005 --------- -------- 050

0127plusmn00062 0115plusmn00064 008plusmn0012 0117plusmn0004 0088plusmn00054 0122plusmn0008 008plusmn0017 0126plusmn0028 0039plusmn0005 0122plusmn0004 1

018plusmn0008 0185plusmn0010 021plusmn0004 017plusmn0004 0182plusmn0054 0179plusmn0006 0112plusmn00025 0193plusmn0012 0097plusmn0020 019plusmn0004 2

0357plusmn0020 0425plusmn0005 033plusmn0021 045plusmn0009 0285plusmn0082 0494plusmn0015 0395plusmn0016 0572plusmn001 0415plusmn0017 054plusmn0027 4

018plusmn0015 016plusmn0016 0207plusmn0022 0175plusmn0006 0257plusmn0037 0180plusmn0017 0272plusmn0015 0201plusmn003 0196plusmn0016 0222plusmn0002 6

0212plusmn0033 0212plusmn0020 0200plusmn0044 0122plusmn0024 0152plusmn0011 014plusmn0022 0122plusmn00062 0102plusmn0001 0107plusmn00094 0117plusmn0002 8

0372plusmn0042 025plusmn001 0325plusmn0027 0192plusmn0014 0265plusmn00064 0185plusmn0015 0272plusmn0125 0195plusmn0012 0252plusmn0032 0275plusmn0009 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

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Table (5) The amount of urine (mlmin) voided in normal and experimentally Salmonella typhimurim infected goats following

repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)

Dose Time of a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

plusmn00372344 126plusmn0034 130plusmn0030 130plusmn0028 118plusmn0066 118plusmn0067 108plusmn0013 108plusmn0008 ----------- -------- Before

0577plusmn0069 43494057plusmn 045plusmn0060 plusmn0064309 0312plusmn002 033plusmn0012 0340plusmn0024 033plusmn0012 0287plusmn0017 0272plusmn0014 050

0712plusmn0019 0692plusmn0014 068plusmn0081 0697plusmn0006 0672plusmn0011 0675plusmn 0009 0635plusmn0032 0655plusmn0010 0719plusmn0031 0697plusmn0015 1

0837plusmn0025 0787plusmn0021 0732plusmn0011 plusmn00054300 0715plusmn0011 0715plusmn002 0722plusmn0019 0702plusmn0018 0737plusmn0027 0762plusmn0041 2

0535plusmn0095 0507plusmn0021 0447plusmn0022 0452plusmn002 0402plusmn0075 0405plusmn0011 0400plusmn0057 0397plusmn0009 0380plusmn0004 038plusmn001 4

0437plusmn00094 0432plusmn0008 0400plusmn0010 0405plusmn0002 0380plusmn0007 plusmn00044319 0372plusmn0047 037plusmn 0007 0350plusmn0005 0365plusmn0006 6

0397plusmn0028 0410plusmn0008 0380plusmn0012 0395plusmn0009 0355plusmn0086 0352plusmn0007 0340plusmn0004 0345plusmn0005 0302plusmn0004 0335plusmn0005 8

0385plusmn001 0380plusmn0010 0385plusmn00064 0380plusmn0008 0365plusmn0064 0367plusmn0004 0362plusmn0086 0372plusmn0106 0327plusmn0006 0362plusmn0016 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (6) Urine concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats

following repeated intramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)

Dose Time of a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1125plusmn150 1125plusmn15 735plusmn287 81plusmn324 183plusmn03 555plusmn798 37plusmn0811 1815plusmn43290 -------------- ------ Before

2415plusmn357 2625plusmn374 1695plusmn788 249plusmn574 10575plusmn64 2415plusmn357 5400plusmn273 2085plusmn991 102plusmn160 168plusmn547 050

26025plusmn787 2923plusmn479 22425plusmn1225 2805plusmn35 1695plusmn618 2705plusmn471 10200plusmn547 2415plusmn357 6975plusmn225 22425plusmn894 1

29295plusmn765 3012plusmn346 28575plusmn738 2964plusmn415 2355plusmn259 2923plusmn479 1635plusmn561 2645plusmn917 102plusmn547 24825plusmn616 2

23475plusmn430 2482plusmn616 23475plusmn1564 2415plusmn357 1695plusmn788 198plusmn848 8475plusmn309 1515plusmn708 60plusmn212 1185plusmn45 4

1905plusmn45 2355plusmn259 153plusmn519 1935plusmn960 114plusmn948 159plusmn173 6675plusmn309 1215plusmn45 1312plusmn0552 855plusmn193 6

153plusmn1024 1965plusmn135 1335plusmn1229 150plusmn34 735plusmn295 1365plusmn665 6181plusmn339 72plusmn244 907plusmn0951 5025plusmn143 8

135plusmn519 120plusmn346 11725plusmn1551 96plusmn874 525plusmn295 75plusmn173 153plusmn130 39plusmn212 3735plusmn0458 13125plusmn0552 12

Between normal and diseased

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (7) Urineserum concentrations ratios of ceftriaxone following repeated ntramuscular injection of 20 mg

ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats

(n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

229plusmn 163 1448plusmn0743 1885plusmn159 1125plusmn0484 533plusmn0260 1050plusmn358 175plusmn0380 4146plusmn116 ------- ------ Before

741plusmn0063 plusmn01553 58plusmn0242 plusmn0149390 422plusmn0206 683plusmn0106 245plusmn0092 667plusmn0306 0510plusmn0081 559plusmn0181 050

651plusmn0243 plusmn0065031 637plusmn0373 plusmn014431 565plusmn0243 plusmn0085300 360plusmn0303 plusmn0110312 279plusmn0121 534plusmn0248 1

836plusmn0150 plusmn00476322 862plusmn0180 plusmn010463 942plusmn0166 plusmn0130631 217plusmn0303 727plusmn0256 508plusmn0186 plusmn01680340 2

939plusmn0235 plusmn01580344 1006plusmn0710 plusmn00750310 999plusmn0542 plusmn02850344 565plusmn0223 641plusmn0241 48plusmn0164 plusmn014834 4

1005plusmn0418 2plusmn018813 1097plusmn0641 plusmn03979300 993plusmn0921 plusmn0252931 619plusmn0483 plusmn0362933 167plusmn0101 642plusmn0644 6

1091plusmn0649 plusmn075332339 1171plusmn0980 995plusmn0415 925plusmn0593 plusmn05593433 886plusmn0408 plusmn02510311 2055plusmn0311 plusmn02046310 8

2392plusmn129 plusmn032731396 1794plusmn0228 1222plusmn124 1418plusmn109 plusmn026733336 580plusmn0397 plusmn03951326 227plusmn0452 plusmn02740316 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (8) Creatinine clearance (mlmin10kgbwt) following repeated intramuscular injection of 20 mg ceftriaxonekgbwt

twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats (n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1115plusmn0703 2265plusmn167 481plusmn0409 672plusmn0817 669plusmn0672 1202plusmn0777 695plusmn0634 1724plusmn179 ----------- ------ Before

0703plusmn0091 147plusmn0305 0718plusmn0141 251plusmn0707 0547plusmn0055 0699plusmn0092 0802plusmn0099 103plusmn0106 295plusmn0124 0458plusmn0037 050

101plusmn0075 161plusmn0093 131plusmn0099 264plusmn0217 161plusmn0146 373plusmn0499 247plusmn0110 4755plusmn0582 214plusmn0234 103plusmn0166 1

157plusmn0198 387plusmn0340 173plusmn0501 267plusmn0217 187plusmn0563 287plusmn0499 451plusmn0223 972plusmn105 263plusmn0399 169plusmn0454 2

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

184plusmn0095 346plusmn0444 173plusmn0501 436plusmn0599 383plusmn0299 682plusmn0584 328plusmn0253 119plusmn153 123plusmn0057 292plusmn0742 4

221plusmn0242 411plusmn0661 241plusmn0186 663plusmn0584 308plusmn0234 422plusmn0314 353plusmn0393 548plusmn0901 105plusmn0057 264plusmn0294 6

261plusmn0295 476plusmn0339 319plusmn0273 753plusmn0676 106plusmn0207 0773plusmn0049 228plusmn0175 456plusmn0340 206plusmn0160 404plusmn0419 8

310plusmn0218 409plusmn0434 3264plusmn0153 669plusmn0476 209plusmn0189 235plusmn0337 217plusmn0143 377plusmn0342 240plusmn0218 6055plusmn0176 12

Between normal and diseased

Plt 005 Plt001 Plt0001

Table (9) Ceftriaxone clearance (mlmin10kgbwt following repeated intramuscular injection of 20 mg ceftriaxone kgbwt

twice in normal and experimentally Salmonella typhimurim infected goats (n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1048plusmn121 0557plusmn684 895plusmn113 0547plusmn560 238plusmn0222 103plusmn 480 0668plusmn0157 0173plusmn216 -------- ----------- Before

156plusmn0251 43204plusmn3322 0936plusmn0162 43211plusmn3334 0473plusmn0037 43469plusmn43964 0300plusmn0028 43341plusmn080 0190plusmn0137 43400plusmn43642 050

166plusmn0079 43323plusmn3311 157plusmn0178 43419plusmn3301 137plusmn0115 43311plusmn33022 0883plusmn0054 43341plusmn 133 0616plusmn0153 43120plusmn3301 1

254plusmn0272 43361plusmn3391 222plusmn0093 4331plusmn3390 243plusmn0180 43209plusmn3309 183plusmn0149 43310plusmn2340 128plusmn0153 43312plusmn3390 2

181plusmn0136 43339plusmn3316 161plusmn0129 433plusmn3329 144plusmn0100 43412plusmn3349 0821plusmn0072 0063plusmn0977 0654plusmn0065 43400plusmn4306 4

160plusmn0177 43393plusmn336 152plusmn0200 43416plusmn331 135plusmn0118 4332plusmn3322 0897plusmn0052 43304plusmn3330 0212plusmn0022 43460plusmn43112 6

153plusmn0049 43291plusmn234 163plusmn0242 43346plusmn3300 0891plusmn0272 43306plusmn3310 108plusmn0071 43416plusmn04310 0229plusmn0046 43490plusmn43916 8

340plusmn0522 43214plusmn2341 249plusmn0150 43112plusmn3393 186plusmn0159 43320plusmn336 0773plusmn0094 43390plusmn 134 0264plusmn0043 43400plusmn 54369 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

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Table (10) Ceftriaxone clearancecreatinine clearance following repeated ntramuscular injection of 20 mg

ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats

(n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

0934plusmn0083 0305plusmn0013 183plusmn0116 0864plusmn0098 0358plusmn0018 0279plusmn0047 0099plusmn0020 0127plusmn0001 ------- ----------- Before

220plusmn0115 0819plusmn0044 131plusmn00414 0458plusmn0029 0876plusmn0063 126plusmn0068 0361plusmn0011 0813plusmn0031 0018plusmn0003 108plusmn0062 050

164plusmn0078 0818plusmn0029 118plusmn0068 0546plusmn0027 0858plusmn0052 0407plusmn0041 0331plusmn0009 0287plusmn0025 0324plusmn0011 0909plusmn0187 1

161plusmn0044 0488plusmn0005 232plusmn128 0329plusmn0027 169plusmn0464 0686plusmn0050 0409plusmn0020 0220plusmn0029 0512plusmn0077 266plusmn177 2

0933plusmn0024 0394plusmn0005 0948plusmn0062 0296plusmn0007 0381plusmn0027 0160plusmn0008 0235plusmn0014 0083plusmn0006 0528plusmn0028 0362plusmn0041 4

0726plusmn0018 0411plusmn0028 0639plusmn0066 0204plusmn0006 0446plusmn0034 0286plusmn0008 0238plusmn0019 0214plusmn0006 020plusmn0013 0382plusmn0028 6

0609plusmn0072 0425plusmn0036 0508plusmn0052 0192plusmn0009 0524plusmn0146 174plusmn0083 0477plusmn0015 0213plusmn00018 0109plusmn0185 0222plusmn0006 8

108plusmn0128 0496plusmn0012 0942plusmn0004 0265plusmn0030 0891plusmn0056 0706plusmn0103 0351plusmn0022 0354plusmn0018 0111plusmn0021 0098plusmn0018 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

DISCUSSION

In the present investigation intravenous injection of 20 mg ceftriaxonekgbwt in normal goats the drug showed high serum level

(92plusmn 0408 μgml) at 5 minutes post-injection then its concentration was decreased gradually till reached its minimum level (18

plusmn0816μgml) at 8hours post-injection

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

In the present investigation the intravenous injection of 20 mg ceftriaxonekgbwt In normal

goats showed that the drug disposition best fitted a two-compartments- open model a

compartment of plasma and rapid equilibrating tissues and a deeper slower compartment

The obtained result is consistent with those reported for ceftriaxone in lactating goats[9]

lactating ewe[25]

domestic cat[15]

calves[26]

and patanwadi sheep[8]

Also this phenomenon is

in agreement with those reported for other cephalosporines as ceftazidime in a rabbit[27]

cefepime in dog and neonatal foals[28]

ewes[29]

ceftriaxone in goats[9]

cefipime in calves[30]

ceftiofur in cross-bred friesian cattle[31]

cefipime in calves[32]

ceftiofur in cows[33]

cefpirome

in cross-bred calves[3]

cefazidime in goats[35]

and cefquinome in sheep and goats[36]

cefipime

in chickens[37]

Ceftriaxone was distributed after intravenous injection with a distribution phase (α) equal to

656 per hour with a short distribution half ndash life [t05 (α)] equal to 0104 hour The shorter

distribution half-life of ceftriaxone in goats suggested the rapid distribution of the drug in

body tissue and fluid and that nearly similar to that recorded for ceftriaxone in lactating

goats(012 hour)[9]

for ceftriaxone in lactating ewes (0152 hour)[2]

and for ceftriaxone in

calves( 013hour)[26]

The rapid distribution of ceftriaxone in goats is supported by high rate constant of transfer of

the drug from central to peripheral compartment [K12 = 353 h-1

] as compared to the rate

constant of transfer of the drug from peripheral to central compartment [K21= 295 h-1

] This

value is nearly similar to those reported for cefotaxime in goats (K21=327 h-1

)[38]

On contrast

this value was higher than those recorded for ceftriaxone in lactating goats (K21=143 h-1

)[9]

in

lactating ewes (K21=125 h-1

)[25]

and in domestic cats (K21=154 h-1

)[15]

The apparent volume of distribution of ceftriaxone was (0355plusmn0004LKg) this value is

nearly similar to that recorded for cefaronide in sheep(039 LKg)[7]

cefotaxime in dog (048

lkg)[39]

in goat (051 lkg)

[40] for caphalexin in buffalo calves (041 Lkg)

[41] for cefipime in

ewes and calves (032 lkg) (043Lkg)[29]

and[30]

respectively For ceftriaxone in domestic

cats (057Lkg)[15]

in camel (032Lkg)[42]

On the other hand this result is differ than that

reported for cefotaxime in buffalo calves (117Lkg)[43]

High value of the volume of

distribution suggested extensive penetration power Drug with volume of distribution greater

than one literkilogram indicated wide distribution or extensive tissue binding or both[44]

The

apparent volume of distribution in the present study indicated moderate tissue penetrating

power This result agreed with[15]

for ceftriaxone in domestic cats

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

Ceftriaxone is eliminated in the current study following a single intravenous injection with

elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the

data recorded for ceftizoxime in goats (624hours)[45]

On contrast this value was longer than

that reported for ceftriaxone in lactating ewe (175hours)[25]

for cefaronide in sheep (17

hours)[7]

For cephalexin in buffulo calves (216hours)[41]

for ceftriaxone in healthy horse

(162hours)[46]

also this value is longer than that recorded for ceftriaxone in lactating goats

(144hours)[9]

for cefipime in goats (186hours)[47]

The rate of total body clearance of ceftriaxone following a single intravenous injection is

0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]

On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating

goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)

(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]

respectively

The variation in total body clearance might be attributed to specific interspecies variation

handling of the drug method used healthy status of the animal[48]

The difference between values calculated for pharmacokinetic parameters may be attributed

to animal species the drug formulation employed the age the size or sex o l lf the animal

or even inter individual variation and also due to method of analysis of the drug[49]

Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the

drug reached its peak serum concentrations after one hour of injection with value

of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12

hours post-injection The reported peak serum concentrations neerly similar to that reported

for cephalexin in buffulo calves (457 microgml)[41]

These results is differed than those reported

for ceftriaxone in cross breed calves (188 microgml at 30 min[16]

in Kangro breed of goats

(Capra Hircus) (2640 microgml at 20 min[10][50]

found after intramuscular administration of

ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher

than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]

The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time

(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats

(4932 microgml[47]

The reported maximum serum concentration (Cmax) is higher than that

reported for ceftriaxone in lactating goats(236 microgml)[9]

in lactating ewes (1722 microgml[25]

in

wwwwjppscom Vol 5 Issue 01 2016

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

goats (2151 microgml)[11]

for cefquinome in camels (123 microgml)[51]

for ceftriaxone in calves

(1534 microgml)[26]

in patanwadi sheep (1553 microgml)[8]

for cefpirome in cattle (101 microgml)[52]

And for ceftiofur in chickens (2594 μgml)[37]

On the other hand the result was lower than

that reported by[6]

who observed the maximum serum concentration (Cmax) of ceftriaxone in

human after ntramuscular administration was (805 microgml) also it was lower than that

reported for ceftriaxone in dog (11510 microgml)[53]

in domestic cats (5440 microgml)[15]

and for

ceftazoxime in goats (8878 microgml)[45]

The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating

ewes by[25]

On contrast it is longer than those reported for ceftriaxone in dogs

(129hours)[53]

for ceftriaxone in lactating goats (07hours)[9]

also the result was longer than

that reported for ceftriaxone in domestic cats (033hours)[15]

in buffulo calves (05 hours)[13]

and for cefpirome in cattle (075hours)[52]

The reported [tmax] is shorter than those reported

for cefquinome in camels (425hours)[51]

in sheep and goats (261 and 262 hours)[36]

and for

ceftiofur in chickens (251 hours)[37]

The elimination half life [t05(β)]

following a single intramuscular administration was 1804 hours This value is nearly agreed

with that recorded for cefquinomein camels (1024hours)[52]

On contrast this result is longer

than that reported for cephalexin in buffalo calves (243hours)[41]

for ceftriaxone in lactating

ewes (177hours)[25]

in buffalo calves (438hours)[13]

in goats (203 hours)[11]

and for

cefipime in goats (165 hours)[47]

The rate of total body clearance of ceftriaxone following a single intramuscular injection is

0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves

(401Lkgh)[13]

in goats (304 Lkgh)[11]

and in sheep (222 Lkgh)[8]

Bioavailability is the fraction of the drug administered by non vascular rout that gains

accesses to the systemic circulation The obtained result revealed that the calculated systemic

bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves

(61)[54]

It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]

On the other

hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]

for ceftriaxone in goats (59)[11]

in calves (47)[55]

On contrast this value is lower than

those reported for cefotaxime in two cats 982 and 93)[57]

for cephradine in goats

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

(739)[58]

for ceftazidime in a rabbit (966)[27]

for ceftriaxone in lactating goats (85)[9]

in lactating ewes (836)[25]

in domestic cats 8572[15]

for cefipime in goats 8645[47]

for ceftriaxone in buffulo calves 702[13]

and for ceftiofur in chickens 8890[37]

Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium

infected goats twics dialy for five days revealed that the drug could be detected in a

therapeutic level for 12hours following repeated intramuscular administrations and exceeded

the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]

The relative higher serum concentrations of ceftriaxone after the last dose compared to the

first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12

hours intervals for five consecutive days These observations agreed with data reported by[36]

on comparing the data of serum levels of repeated intramuscular injections with first

intramuscular injection it was revealed that repeated intramuscular injections of cefquinome

have cumulative effect in both species sheep and goats

The obtained result is inconsistent with that reported by[56]

who found thatwhen cefotaxime

was administered repetitively in patients the ratio of maximal serum levels after the last dose

to those after the first dose demonstrated minimal accumulation of intact drug and by[60]

who

found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in

buffalo calves

The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium

infected goats are significantly lower than those in normal goats following repeated

intramuscular injection These lower blood concentrations in Salmonella typhimurium

infected goats might be attributed to the higher penetrating power of ceftriaxone to the

diseased tissues[48]

This phenomenon is similar to data recorded by[61]

who suggested that

Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of

ceftriaxone These alterations might be due to fever and inflammation induced by

infections[59]

proved that the serum concentrations of cephradine following intramuscular

administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after

each intramuscular dose with a lower significant values recorded in Escherichia-coli infected

goats than in normal goatsAlso similer to that reported by[62]

who observed that the

maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep

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1451

Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

in comparison to normal sheepOn contrast[43]

reported that peak plasma level of cefotaxime

in febrile buffalo calves was higher than healthy buffalo calves

In this study the total body clearance (CLtot) in normal goats are significantly lower than in

Salmonella typhimurium infected goats This result supported by[61]

and[63]

fever and

inflammation are cardinal features in bacterial infection which may in turn caused an

increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all

these could lead to increased in the rate at which the drug was delivered to both organs which

were important sites of drug excretion This might somewhat explain the increase in the total

body clearance in infected goats This result is differ than that reported by[64]

who observed

that the clearance of ceftriaxone was significantly reduced in infected mice than in non

infected animals

The highest concentrations of ceftriaxone in milk are recorded 4 hours after each

intramuscular injection with a significant lower value in Salmonella typhimurium infected

goats than in normal goats This might be attributed to accumulation of drug in the inflammed

tissues[48]

This result is similar to those reported by[6559]

who found that milk concentrations

of gentamicin and cephradine were significantly lower in infected goats and cattle than in

normal ones respectively

The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the

non-ionic passive diffusion principle[66]

reported that most drug cross-lipid membranes by

passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly

influenced by the physicochemical properties of the drug[6768]

Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum

ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the

physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]

Milk

contains substantially more lipid and less protein than serum and is slightly more acidic

Therefore drugs which tend to concentrated in milk are weak bases with low serum protein

binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide

and aminothiazole also possesses an hydroxytriazinone group as new and additional

ionization center[70]

these compounds are sufficiently lipid- soluble to be able to penetrate

tissues

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

The dose of ceftriaxone used in the present study induced therapeutically concentrations in

milk These concentrations suggested that ceftriaxone would be efficacious in treatment of

mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily

for 3-5 days

The study showed that the urine concentrations of ceftriaxone are greater than the concurrent

serum concentrations following intramuscular injection This observation is similar to those

reported in cows after cephapirin administrations[71]

In the present study urine concentrations of ceftriaxone increased with the repetition of

dosing This observation supported by[72]

after repeated intramuscular administrations of

ceftriaxone in healthy volunteeres

The mean peak urine concentrations of ceftriaxone were reached 2 hours after each

intramuscular injection The lower urine ceftriaxone concentrations in Salmonella

typhimurium infected goats than in normal goats might be attributed to the accumulation of

the drug in the inflamed tissues[48]

The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower

ratio in Salmonella typhimurium infected goats than in normal goats at different time of

sampling This indicates that glomerular filteration seemed to be the main pathway of

ceftriaxone elimination This observation supported by[59]

who found that the ratio between

cephradine clearance from blood of goats to creatinine clearance showed a marked decrease

in Escherichia-coli infected goats than in normal goats This indicated that glomerular

filteration seemed to be the main pathway of cephradine elimination with a limited rate of

tubular reabsorption

CONCLUSION

The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value

referred a better absorption of ceftriaxone from its site of intramuscular administration The

high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular

administrations suggested that ceftriaxone could be used for treatment of mastitis caused by

Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats

The high concentrations of ceftriaxone in urine after repeated intramuscular administrations

suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in

goats

REFERANCES

1 Neu HC Merpol NJ and Fukp (1981) Antibacterial activity of ceftriaxone

abetalactamase stable cephalosporines Antimicrobial agents and chemotherapy 19

414-423

2 Richard DM Heel RC Brogden RN Speight TM Avery GS (1984) Ceftriaxone a

review of its antibacterial activity pharmacological properties and therapeutic uses

Drugs 27 469-527

3 Brogden RN and Ward A (1988) Ceftriaxone a reappraisal of its antibacterial activity

and pharmacokinetic properties and an update on its therapeutic use with particular

reference to once-daily administration Drugs 35 604-645

4 Waxman DJ and Strominger JL (1983) Penicillin-binding proteins and the

mechanism of action of beta-lactam antibiotics Annu Rev Biochem 52(1) 825-869

5 Christ W (1991) properties of cephalosporines Infestion 19 244-252

6 Goonetilleke AK Dev D Aziz I Hughes C Smith MJ Basran GS (1996) A

comparative analysis of pharmacokinetics of ceftriaxone in serum and pleural fluid in

humans a study of once daily administration by intramuscular intravenous routes J

Antimicrob Chemother Dec 38(6) 969-76

7 Guerrini VH Filippich LJ Cao G R English PB Bourne DW (1985)

Pharmacokinetics of cefaronide ceftriaxone and cefperazone in sheep J Vet Pharmacol

Ther 8(2) 120-7

8 Swati Tiwari S Patel UD Bhavsar SK and Thaker AM (2010) Pharmacokinetics

and Bioavailability of Ceftriaxone in Patanwadi Sheep Online veterinary journal 5(2)

9 Ismail MM (2005) Pharmacokinetics urinary and mammary excretion of ceftriaxone in

lactating goats J Vet Med A Physiol Pathol Clin Med Sep 52(7) 354-8

10 Rajinder R prawez S Srivastiva AS (2005) Pharmacokinetics and dosage regimen of

ceftriaxone following its single ntramuscular adminsteration in kagani breed of goats

(Capra Hircus) Journal of reaserch 4(2) 91-93

11 Tiwari S Swati Bhavsar SK Patel UD and Thaker AM (2009) Disposition of

Ceftriaxone in Goats (Capra hircus) Online veterinary journal 4(2)

12 Dardi MS Sharma SK and Srivastava AK (2004) Pharmacokinetics and Dosage

regimen of ceftriaxone in buffalo calves Vet Res Commun 28 331-338

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

350plusmn0353 400plusmn0408 300plusmn0408 392plusmn0125 300plusmn0408 35plusmn0353 275plusmn006 300plusmn0408 155plusmn0132 275plusmn0061 6

300 plusmn0408 35plusmn0353 125plusmn0104 200plusmn0408 125plusmn0104 155plusmn01 0825plusmn0062 100plusmn000 0500plusmn0040 0887plusmn0013 8

200plusmn0408 22plusmn0108 100plusmn000 155plusmn0132 100plusmn000 125plusmn0104 0730plusmn002 0825plusmn0078 0422plusmn000 073plusmn0020 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (4) Milkserum concentrations ratios of ceftriaxone in normal and experimentally Salmonella typhimurim infected

goats following repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice daily for five consecutive days (n=4)

Dose Time of

a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

0400plusmn0049 025plusmn0063 0307plusmn0026 021plusmn0019 0365plusmn00064 016plusmn0026 0232plusmn0016 0205plusmn0002 -------- helliphelliphelliphellip Before

0057plusmn0125 0042plusmn00025 0062plusmn00062 0042plusmn0010 0575plusmn00062 0055plusmn0006 0067plusmn0016 0049plusmn0005 --------- -------- 050

0127plusmn00062 0115plusmn00064 008plusmn0012 0117plusmn0004 0088plusmn00054 0122plusmn0008 008plusmn0017 0126plusmn0028 0039plusmn0005 0122plusmn0004 1

018plusmn0008 0185plusmn0010 021plusmn0004 017plusmn0004 0182plusmn0054 0179plusmn0006 0112plusmn00025 0193plusmn0012 0097plusmn0020 019plusmn0004 2

0357plusmn0020 0425plusmn0005 033plusmn0021 045plusmn0009 0285plusmn0082 0494plusmn0015 0395plusmn0016 0572plusmn001 0415plusmn0017 054plusmn0027 4

018plusmn0015 016plusmn0016 0207plusmn0022 0175plusmn0006 0257plusmn0037 0180plusmn0017 0272plusmn0015 0201plusmn003 0196plusmn0016 0222plusmn0002 6

0212plusmn0033 0212plusmn0020 0200plusmn0044 0122plusmn0024 0152plusmn0011 014plusmn0022 0122plusmn00062 0102plusmn0001 0107plusmn00094 0117plusmn0002 8

0372plusmn0042 025plusmn001 0325plusmn0027 0192plusmn0014 0265plusmn00064 0185plusmn0015 0272plusmn0125 0195plusmn0012 0252plusmn0032 0275plusmn0009 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Table (5) The amount of urine (mlmin) voided in normal and experimentally Salmonella typhimurim infected goats following

repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)

Dose Time of a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

plusmn00372344 126plusmn0034 130plusmn0030 130plusmn0028 118plusmn0066 118plusmn0067 108plusmn0013 108plusmn0008 ----------- -------- Before

0577plusmn0069 43494057plusmn 045plusmn0060 plusmn0064309 0312plusmn002 033plusmn0012 0340plusmn0024 033plusmn0012 0287plusmn0017 0272plusmn0014 050

0712plusmn0019 0692plusmn0014 068plusmn0081 0697plusmn0006 0672plusmn0011 0675plusmn 0009 0635plusmn0032 0655plusmn0010 0719plusmn0031 0697plusmn0015 1

0837plusmn0025 0787plusmn0021 0732plusmn0011 plusmn00054300 0715plusmn0011 0715plusmn002 0722plusmn0019 0702plusmn0018 0737plusmn0027 0762plusmn0041 2

0535plusmn0095 0507plusmn0021 0447plusmn0022 0452plusmn002 0402plusmn0075 0405plusmn0011 0400plusmn0057 0397plusmn0009 0380plusmn0004 038plusmn001 4

0437plusmn00094 0432plusmn0008 0400plusmn0010 0405plusmn0002 0380plusmn0007 plusmn00044319 0372plusmn0047 037plusmn 0007 0350plusmn0005 0365plusmn0006 6

0397plusmn0028 0410plusmn0008 0380plusmn0012 0395plusmn0009 0355plusmn0086 0352plusmn0007 0340plusmn0004 0345plusmn0005 0302plusmn0004 0335plusmn0005 8

0385plusmn001 0380plusmn0010 0385plusmn00064 0380plusmn0008 0365plusmn0064 0367plusmn0004 0362plusmn0086 0372plusmn0106 0327plusmn0006 0362plusmn0016 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (6) Urine concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats

following repeated intramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)

Dose Time of a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1125plusmn150 1125plusmn15 735plusmn287 81plusmn324 183plusmn03 555plusmn798 37plusmn0811 1815plusmn43290 -------------- ------ Before

2415plusmn357 2625plusmn374 1695plusmn788 249plusmn574 10575plusmn64 2415plusmn357 5400plusmn273 2085plusmn991 102plusmn160 168plusmn547 050

26025plusmn787 2923plusmn479 22425plusmn1225 2805plusmn35 1695plusmn618 2705plusmn471 10200plusmn547 2415plusmn357 6975plusmn225 22425plusmn894 1

29295plusmn765 3012plusmn346 28575plusmn738 2964plusmn415 2355plusmn259 2923plusmn479 1635plusmn561 2645plusmn917 102plusmn547 24825plusmn616 2

23475plusmn430 2482plusmn616 23475plusmn1564 2415plusmn357 1695plusmn788 198plusmn848 8475plusmn309 1515plusmn708 60plusmn212 1185plusmn45 4

1905plusmn45 2355plusmn259 153plusmn519 1935plusmn960 114plusmn948 159plusmn173 6675plusmn309 1215plusmn45 1312plusmn0552 855plusmn193 6

153plusmn1024 1965plusmn135 1335plusmn1229 150plusmn34 735plusmn295 1365plusmn665 6181plusmn339 72plusmn244 907plusmn0951 5025plusmn143 8

135plusmn519 120plusmn346 11725plusmn1551 96plusmn874 525plusmn295 75plusmn173 153plusmn130 39plusmn212 3735plusmn0458 13125plusmn0552 12

Between normal and diseased

wwwwjppscom Vol 5 Issue 02 2016

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (7) Urineserum concentrations ratios of ceftriaxone following repeated ntramuscular injection of 20 mg

ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats

(n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

229plusmn 163 1448plusmn0743 1885plusmn159 1125plusmn0484 533plusmn0260 1050plusmn358 175plusmn0380 4146plusmn116 ------- ------ Before

741plusmn0063 plusmn01553 58plusmn0242 plusmn0149390 422plusmn0206 683plusmn0106 245plusmn0092 667plusmn0306 0510plusmn0081 559plusmn0181 050

651plusmn0243 plusmn0065031 637plusmn0373 plusmn014431 565plusmn0243 plusmn0085300 360plusmn0303 plusmn0110312 279plusmn0121 534plusmn0248 1

836plusmn0150 plusmn00476322 862plusmn0180 plusmn010463 942plusmn0166 plusmn0130631 217plusmn0303 727plusmn0256 508plusmn0186 plusmn01680340 2

939plusmn0235 plusmn01580344 1006plusmn0710 plusmn00750310 999plusmn0542 plusmn02850344 565plusmn0223 641plusmn0241 48plusmn0164 plusmn014834 4

1005plusmn0418 2plusmn018813 1097plusmn0641 plusmn03979300 993plusmn0921 plusmn0252931 619plusmn0483 plusmn0362933 167plusmn0101 642plusmn0644 6

1091plusmn0649 plusmn075332339 1171plusmn0980 995plusmn0415 925plusmn0593 plusmn05593433 886plusmn0408 plusmn02510311 2055plusmn0311 plusmn02046310 8

2392plusmn129 plusmn032731396 1794plusmn0228 1222plusmn124 1418plusmn109 plusmn026733336 580plusmn0397 plusmn03951326 227plusmn0452 plusmn02740316 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (8) Creatinine clearance (mlmin10kgbwt) following repeated intramuscular injection of 20 mg ceftriaxonekgbwt

twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats (n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1115plusmn0703 2265plusmn167 481plusmn0409 672plusmn0817 669plusmn0672 1202plusmn0777 695plusmn0634 1724plusmn179 ----------- ------ Before

0703plusmn0091 147plusmn0305 0718plusmn0141 251plusmn0707 0547plusmn0055 0699plusmn0092 0802plusmn0099 103plusmn0106 295plusmn0124 0458plusmn0037 050

101plusmn0075 161plusmn0093 131plusmn0099 264plusmn0217 161plusmn0146 373plusmn0499 247plusmn0110 4755plusmn0582 214plusmn0234 103plusmn0166 1

157plusmn0198 387plusmn0340 173plusmn0501 267plusmn0217 187plusmn0563 287plusmn0499 451plusmn0223 972plusmn105 263plusmn0399 169plusmn0454 2

wwwwjppscom Vol 5 Issue 02 2016

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

184plusmn0095 346plusmn0444 173plusmn0501 436plusmn0599 383plusmn0299 682plusmn0584 328plusmn0253 119plusmn153 123plusmn0057 292plusmn0742 4

221plusmn0242 411plusmn0661 241plusmn0186 663plusmn0584 308plusmn0234 422plusmn0314 353plusmn0393 548plusmn0901 105plusmn0057 264plusmn0294 6

261plusmn0295 476plusmn0339 319plusmn0273 753plusmn0676 106plusmn0207 0773plusmn0049 228plusmn0175 456plusmn0340 206plusmn0160 404plusmn0419 8

310plusmn0218 409plusmn0434 3264plusmn0153 669plusmn0476 209plusmn0189 235plusmn0337 217plusmn0143 377plusmn0342 240plusmn0218 6055plusmn0176 12

Between normal and diseased

Plt 005 Plt001 Plt0001

Table (9) Ceftriaxone clearance (mlmin10kgbwt following repeated intramuscular injection of 20 mg ceftriaxone kgbwt

twice in normal and experimentally Salmonella typhimurim infected goats (n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1048plusmn121 0557plusmn684 895plusmn113 0547plusmn560 238plusmn0222 103plusmn 480 0668plusmn0157 0173plusmn216 -------- ----------- Before

156plusmn0251 43204plusmn3322 0936plusmn0162 43211plusmn3334 0473plusmn0037 43469plusmn43964 0300plusmn0028 43341plusmn080 0190plusmn0137 43400plusmn43642 050

166plusmn0079 43323plusmn3311 157plusmn0178 43419plusmn3301 137plusmn0115 43311plusmn33022 0883plusmn0054 43341plusmn 133 0616plusmn0153 43120plusmn3301 1

254plusmn0272 43361plusmn3391 222plusmn0093 4331plusmn3390 243plusmn0180 43209plusmn3309 183plusmn0149 43310plusmn2340 128plusmn0153 43312plusmn3390 2

181plusmn0136 43339plusmn3316 161plusmn0129 433plusmn3329 144plusmn0100 43412plusmn3349 0821plusmn0072 0063plusmn0977 0654plusmn0065 43400plusmn4306 4

160plusmn0177 43393plusmn336 152plusmn0200 43416plusmn331 135plusmn0118 4332plusmn3322 0897plusmn0052 43304plusmn3330 0212plusmn0022 43460plusmn43112 6

153plusmn0049 43291plusmn234 163plusmn0242 43346plusmn3300 0891plusmn0272 43306plusmn3310 108plusmn0071 43416plusmn04310 0229plusmn0046 43490plusmn43916 8

340plusmn0522 43214plusmn2341 249plusmn0150 43112plusmn3393 186plusmn0159 43320plusmn336 0773plusmn0094 43390plusmn 134 0264plusmn0043 43400plusmn 54369 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Table (10) Ceftriaxone clearancecreatinine clearance following repeated ntramuscular injection of 20 mg

ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats

(n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

0934plusmn0083 0305plusmn0013 183plusmn0116 0864plusmn0098 0358plusmn0018 0279plusmn0047 0099plusmn0020 0127plusmn0001 ------- ----------- Before

220plusmn0115 0819plusmn0044 131plusmn00414 0458plusmn0029 0876plusmn0063 126plusmn0068 0361plusmn0011 0813plusmn0031 0018plusmn0003 108plusmn0062 050

164plusmn0078 0818plusmn0029 118plusmn0068 0546plusmn0027 0858plusmn0052 0407plusmn0041 0331plusmn0009 0287plusmn0025 0324plusmn0011 0909plusmn0187 1

161plusmn0044 0488plusmn0005 232plusmn128 0329plusmn0027 169plusmn0464 0686plusmn0050 0409plusmn0020 0220plusmn0029 0512plusmn0077 266plusmn177 2

0933plusmn0024 0394plusmn0005 0948plusmn0062 0296plusmn0007 0381plusmn0027 0160plusmn0008 0235plusmn0014 0083plusmn0006 0528plusmn0028 0362plusmn0041 4

0726plusmn0018 0411plusmn0028 0639plusmn0066 0204plusmn0006 0446plusmn0034 0286plusmn0008 0238plusmn0019 0214plusmn0006 020plusmn0013 0382plusmn0028 6

0609plusmn0072 0425plusmn0036 0508plusmn0052 0192plusmn0009 0524plusmn0146 174plusmn0083 0477plusmn0015 0213plusmn00018 0109plusmn0185 0222plusmn0006 8

108plusmn0128 0496plusmn0012 0942plusmn0004 0265plusmn0030 0891plusmn0056 0706plusmn0103 0351plusmn0022 0354plusmn0018 0111plusmn0021 0098plusmn0018 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

DISCUSSION

In the present investigation intravenous injection of 20 mg ceftriaxonekgbwt in normal goats the drug showed high serum level

(92plusmn 0408 μgml) at 5 minutes post-injection then its concentration was decreased gradually till reached its minimum level (18

plusmn0816μgml) at 8hours post-injection

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

In the present investigation the intravenous injection of 20 mg ceftriaxonekgbwt In normal

goats showed that the drug disposition best fitted a two-compartments- open model a

compartment of plasma and rapid equilibrating tissues and a deeper slower compartment

The obtained result is consistent with those reported for ceftriaxone in lactating goats[9]

lactating ewe[25]

domestic cat[15]

calves[26]

and patanwadi sheep[8]

Also this phenomenon is

in agreement with those reported for other cephalosporines as ceftazidime in a rabbit[27]

cefepime in dog and neonatal foals[28]

ewes[29]

ceftriaxone in goats[9]

cefipime in calves[30]

ceftiofur in cross-bred friesian cattle[31]

cefipime in calves[32]

ceftiofur in cows[33]

cefpirome

in cross-bred calves[3]

cefazidime in goats[35]

and cefquinome in sheep and goats[36]

cefipime

in chickens[37]

Ceftriaxone was distributed after intravenous injection with a distribution phase (α) equal to

656 per hour with a short distribution half ndash life [t05 (α)] equal to 0104 hour The shorter

distribution half-life of ceftriaxone in goats suggested the rapid distribution of the drug in

body tissue and fluid and that nearly similar to that recorded for ceftriaxone in lactating

goats(012 hour)[9]

for ceftriaxone in lactating ewes (0152 hour)[2]

and for ceftriaxone in

calves( 013hour)[26]

The rapid distribution of ceftriaxone in goats is supported by high rate constant of transfer of

the drug from central to peripheral compartment [K12 = 353 h-1

] as compared to the rate

constant of transfer of the drug from peripheral to central compartment [K21= 295 h-1

] This

value is nearly similar to those reported for cefotaxime in goats (K21=327 h-1

)[38]

On contrast

this value was higher than those recorded for ceftriaxone in lactating goats (K21=143 h-1

)[9]

in

lactating ewes (K21=125 h-1

)[25]

and in domestic cats (K21=154 h-1

)[15]

The apparent volume of distribution of ceftriaxone was (0355plusmn0004LKg) this value is

nearly similar to that recorded for cefaronide in sheep(039 LKg)[7]

cefotaxime in dog (048

lkg)[39]

in goat (051 lkg)

[40] for caphalexin in buffalo calves (041 Lkg)

[41] for cefipime in

ewes and calves (032 lkg) (043Lkg)[29]

and[30]

respectively For ceftriaxone in domestic

cats (057Lkg)[15]

in camel (032Lkg)[42]

On the other hand this result is differ than that

reported for cefotaxime in buffalo calves (117Lkg)[43]

High value of the volume of

distribution suggested extensive penetration power Drug with volume of distribution greater

than one literkilogram indicated wide distribution or extensive tissue binding or both[44]

The

apparent volume of distribution in the present study indicated moderate tissue penetrating

power This result agreed with[15]

for ceftriaxone in domestic cats

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

Ceftriaxone is eliminated in the current study following a single intravenous injection with

elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the

data recorded for ceftizoxime in goats (624hours)[45]

On contrast this value was longer than

that reported for ceftriaxone in lactating ewe (175hours)[25]

for cefaronide in sheep (17

hours)[7]

For cephalexin in buffulo calves (216hours)[41]

for ceftriaxone in healthy horse

(162hours)[46]

also this value is longer than that recorded for ceftriaxone in lactating goats

(144hours)[9]

for cefipime in goats (186hours)[47]

The rate of total body clearance of ceftriaxone following a single intravenous injection is

0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]

On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating

goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)

(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]

respectively

The variation in total body clearance might be attributed to specific interspecies variation

handling of the drug method used healthy status of the animal[48]

The difference between values calculated for pharmacokinetic parameters may be attributed

to animal species the drug formulation employed the age the size or sex o l lf the animal

or even inter individual variation and also due to method of analysis of the drug[49]

Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the

drug reached its peak serum concentrations after one hour of injection with value

of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12

hours post-injection The reported peak serum concentrations neerly similar to that reported

for cephalexin in buffulo calves (457 microgml)[41]

These results is differed than those reported

for ceftriaxone in cross breed calves (188 microgml at 30 min[16]

in Kangro breed of goats

(Capra Hircus) (2640 microgml at 20 min[10][50]

found after intramuscular administration of

ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher

than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]

The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time

(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats

(4932 microgml[47]

The reported maximum serum concentration (Cmax) is higher than that

reported for ceftriaxone in lactating goats(236 microgml)[9]

in lactating ewes (1722 microgml[25]

in

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

goats (2151 microgml)[11]

for cefquinome in camels (123 microgml)[51]

for ceftriaxone in calves

(1534 microgml)[26]

in patanwadi sheep (1553 microgml)[8]

for cefpirome in cattle (101 microgml)[52]

And for ceftiofur in chickens (2594 μgml)[37]

On the other hand the result was lower than

that reported by[6]

who observed the maximum serum concentration (Cmax) of ceftriaxone in

human after ntramuscular administration was (805 microgml) also it was lower than that

reported for ceftriaxone in dog (11510 microgml)[53]

in domestic cats (5440 microgml)[15]

and for

ceftazoxime in goats (8878 microgml)[45]

The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating

ewes by[25]

On contrast it is longer than those reported for ceftriaxone in dogs

(129hours)[53]

for ceftriaxone in lactating goats (07hours)[9]

also the result was longer than

that reported for ceftriaxone in domestic cats (033hours)[15]

in buffulo calves (05 hours)[13]

and for cefpirome in cattle (075hours)[52]

The reported [tmax] is shorter than those reported

for cefquinome in camels (425hours)[51]

in sheep and goats (261 and 262 hours)[36]

and for

ceftiofur in chickens (251 hours)[37]

The elimination half life [t05(β)]

following a single intramuscular administration was 1804 hours This value is nearly agreed

with that recorded for cefquinomein camels (1024hours)[52]

On contrast this result is longer

than that reported for cephalexin in buffalo calves (243hours)[41]

for ceftriaxone in lactating

ewes (177hours)[25]

in buffalo calves (438hours)[13]

in goats (203 hours)[11]

and for

cefipime in goats (165 hours)[47]

The rate of total body clearance of ceftriaxone following a single intramuscular injection is

0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves

(401Lkgh)[13]

in goats (304 Lkgh)[11]

and in sheep (222 Lkgh)[8]

Bioavailability is the fraction of the drug administered by non vascular rout that gains

accesses to the systemic circulation The obtained result revealed that the calculated systemic

bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves

(61)[54]

It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]

On the other

hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]

for ceftriaxone in goats (59)[11]

in calves (47)[55]

On contrast this value is lower than

those reported for cefotaxime in two cats 982 and 93)[57]

for cephradine in goats

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

(739)[58]

for ceftazidime in a rabbit (966)[27]

for ceftriaxone in lactating goats (85)[9]

in lactating ewes (836)[25]

in domestic cats 8572[15]

for cefipime in goats 8645[47]

for ceftriaxone in buffulo calves 702[13]

and for ceftiofur in chickens 8890[37]

Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium

infected goats twics dialy for five days revealed that the drug could be detected in a

therapeutic level for 12hours following repeated intramuscular administrations and exceeded

the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]

The relative higher serum concentrations of ceftriaxone after the last dose compared to the

first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12

hours intervals for five consecutive days These observations agreed with data reported by[36]

on comparing the data of serum levels of repeated intramuscular injections with first

intramuscular injection it was revealed that repeated intramuscular injections of cefquinome

have cumulative effect in both species sheep and goats

The obtained result is inconsistent with that reported by[56]

who found thatwhen cefotaxime

was administered repetitively in patients the ratio of maximal serum levels after the last dose

to those after the first dose demonstrated minimal accumulation of intact drug and by[60]

who

found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in

buffalo calves

The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium

infected goats are significantly lower than those in normal goats following repeated

intramuscular injection These lower blood concentrations in Salmonella typhimurium

infected goats might be attributed to the higher penetrating power of ceftriaxone to the

diseased tissues[48]

This phenomenon is similar to data recorded by[61]

who suggested that

Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of

ceftriaxone These alterations might be due to fever and inflammation induced by

infections[59]

proved that the serum concentrations of cephradine following intramuscular

administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after

each intramuscular dose with a lower significant values recorded in Escherichia-coli infected

goats than in normal goatsAlso similer to that reported by[62]

who observed that the

maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep

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1451

Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

in comparison to normal sheepOn contrast[43]

reported that peak plasma level of cefotaxime

in febrile buffalo calves was higher than healthy buffalo calves

In this study the total body clearance (CLtot) in normal goats are significantly lower than in

Salmonella typhimurium infected goats This result supported by[61]

and[63]

fever and

inflammation are cardinal features in bacterial infection which may in turn caused an

increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all

these could lead to increased in the rate at which the drug was delivered to both organs which

were important sites of drug excretion This might somewhat explain the increase in the total

body clearance in infected goats This result is differ than that reported by[64]

who observed

that the clearance of ceftriaxone was significantly reduced in infected mice than in non

infected animals

The highest concentrations of ceftriaxone in milk are recorded 4 hours after each

intramuscular injection with a significant lower value in Salmonella typhimurium infected

goats than in normal goats This might be attributed to accumulation of drug in the inflammed

tissues[48]

This result is similar to those reported by[6559]

who found that milk concentrations

of gentamicin and cephradine were significantly lower in infected goats and cattle than in

normal ones respectively

The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the

non-ionic passive diffusion principle[66]

reported that most drug cross-lipid membranes by

passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly

influenced by the physicochemical properties of the drug[6768]

Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum

ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the

physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]

Milk

contains substantially more lipid and less protein than serum and is slightly more acidic

Therefore drugs which tend to concentrated in milk are weak bases with low serum protein

binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide

and aminothiazole also possesses an hydroxytriazinone group as new and additional

ionization center[70]

these compounds are sufficiently lipid- soluble to be able to penetrate

tissues

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

The dose of ceftriaxone used in the present study induced therapeutically concentrations in

milk These concentrations suggested that ceftriaxone would be efficacious in treatment of

mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily

for 3-5 days

The study showed that the urine concentrations of ceftriaxone are greater than the concurrent

serum concentrations following intramuscular injection This observation is similar to those

reported in cows after cephapirin administrations[71]

In the present study urine concentrations of ceftriaxone increased with the repetition of

dosing This observation supported by[72]

after repeated intramuscular administrations of

ceftriaxone in healthy volunteeres

The mean peak urine concentrations of ceftriaxone were reached 2 hours after each

intramuscular injection The lower urine ceftriaxone concentrations in Salmonella

typhimurium infected goats than in normal goats might be attributed to the accumulation of

the drug in the inflamed tissues[48]

The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower

ratio in Salmonella typhimurium infected goats than in normal goats at different time of

sampling This indicates that glomerular filteration seemed to be the main pathway of

ceftriaxone elimination This observation supported by[59]

who found that the ratio between

cephradine clearance from blood of goats to creatinine clearance showed a marked decrease

in Escherichia-coli infected goats than in normal goats This indicated that glomerular

filteration seemed to be the main pathway of cephradine elimination with a limited rate of

tubular reabsorption

CONCLUSION

The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value

referred a better absorption of ceftriaxone from its site of intramuscular administration The

high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular

administrations suggested that ceftriaxone could be used for treatment of mastitis caused by

Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats

The high concentrations of ceftriaxone in urine after repeated intramuscular administrations

suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections

wwwwjppscom Vol 5 Issue 01 2016

1453

Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in

goats

REFERANCES

1 Neu HC Merpol NJ and Fukp (1981) Antibacterial activity of ceftriaxone

abetalactamase stable cephalosporines Antimicrobial agents and chemotherapy 19

414-423

2 Richard DM Heel RC Brogden RN Speight TM Avery GS (1984) Ceftriaxone a

review of its antibacterial activity pharmacological properties and therapeutic uses

Drugs 27 469-527

3 Brogden RN and Ward A (1988) Ceftriaxone a reappraisal of its antibacterial activity

and pharmacokinetic properties and an update on its therapeutic use with particular

reference to once-daily administration Drugs 35 604-645

4 Waxman DJ and Strominger JL (1983) Penicillin-binding proteins and the

mechanism of action of beta-lactam antibiotics Annu Rev Biochem 52(1) 825-869

5 Christ W (1991) properties of cephalosporines Infestion 19 244-252

6 Goonetilleke AK Dev D Aziz I Hughes C Smith MJ Basran GS (1996) A

comparative analysis of pharmacokinetics of ceftriaxone in serum and pleural fluid in

humans a study of once daily administration by intramuscular intravenous routes J

Antimicrob Chemother Dec 38(6) 969-76

7 Guerrini VH Filippich LJ Cao G R English PB Bourne DW (1985)

Pharmacokinetics of cefaronide ceftriaxone and cefperazone in sheep J Vet Pharmacol

Ther 8(2) 120-7

8 Swati Tiwari S Patel UD Bhavsar SK and Thaker AM (2010) Pharmacokinetics

and Bioavailability of Ceftriaxone in Patanwadi Sheep Online veterinary journal 5(2)

9 Ismail MM (2005) Pharmacokinetics urinary and mammary excretion of ceftriaxone in

lactating goats J Vet Med A Physiol Pathol Clin Med Sep 52(7) 354-8

10 Rajinder R prawez S Srivastiva AS (2005) Pharmacokinetics and dosage regimen of

ceftriaxone following its single ntramuscular adminsteration in kagani breed of goats

(Capra Hircus) Journal of reaserch 4(2) 91-93

11 Tiwari S Swati Bhavsar SK Patel UD and Thaker AM (2009) Disposition of

Ceftriaxone in Goats (Capra hircus) Online veterinary journal 4(2)

12 Dardi MS Sharma SK and Srivastava AK (2004) Pharmacokinetics and Dosage

regimen of ceftriaxone in buffalo calves Vet Res Commun 28 331-338

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Table (5) The amount of urine (mlmin) voided in normal and experimentally Salmonella typhimurim infected goats following

repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)

Dose Time of a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

plusmn00372344 126plusmn0034 130plusmn0030 130plusmn0028 118plusmn0066 118plusmn0067 108plusmn0013 108plusmn0008 ----------- -------- Before

0577plusmn0069 43494057plusmn 045plusmn0060 plusmn0064309 0312plusmn002 033plusmn0012 0340plusmn0024 033plusmn0012 0287plusmn0017 0272plusmn0014 050

0712plusmn0019 0692plusmn0014 068plusmn0081 0697plusmn0006 0672plusmn0011 0675plusmn 0009 0635plusmn0032 0655plusmn0010 0719plusmn0031 0697plusmn0015 1

0837plusmn0025 0787plusmn0021 0732plusmn0011 plusmn00054300 0715plusmn0011 0715plusmn002 0722plusmn0019 0702plusmn0018 0737plusmn0027 0762plusmn0041 2

0535plusmn0095 0507plusmn0021 0447plusmn0022 0452plusmn002 0402plusmn0075 0405plusmn0011 0400plusmn0057 0397plusmn0009 0380plusmn0004 038plusmn001 4

0437plusmn00094 0432plusmn0008 0400plusmn0010 0405plusmn0002 0380plusmn0007 plusmn00044319 0372plusmn0047 037plusmn 0007 0350plusmn0005 0365plusmn0006 6

0397plusmn0028 0410plusmn0008 0380plusmn0012 0395plusmn0009 0355plusmn0086 0352plusmn0007 0340plusmn0004 0345plusmn0005 0302plusmn0004 0335plusmn0005 8

0385plusmn001 0380plusmn0010 0385plusmn00064 0380plusmn0008 0365plusmn0064 0367plusmn0004 0362plusmn0086 0372plusmn0106 0327plusmn0006 0362plusmn0016 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (6) Urine concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats

following repeated intramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)

Dose Time of a

administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1125plusmn150 1125plusmn15 735plusmn287 81plusmn324 183plusmn03 555plusmn798 37plusmn0811 1815plusmn43290 -------------- ------ Before

2415plusmn357 2625plusmn374 1695plusmn788 249plusmn574 10575plusmn64 2415plusmn357 5400plusmn273 2085plusmn991 102plusmn160 168plusmn547 050

26025plusmn787 2923plusmn479 22425plusmn1225 2805plusmn35 1695plusmn618 2705plusmn471 10200plusmn547 2415plusmn357 6975plusmn225 22425plusmn894 1

29295plusmn765 3012plusmn346 28575plusmn738 2964plusmn415 2355plusmn259 2923plusmn479 1635plusmn561 2645plusmn917 102plusmn547 24825plusmn616 2

23475plusmn430 2482plusmn616 23475plusmn1564 2415plusmn357 1695plusmn788 198plusmn848 8475plusmn309 1515plusmn708 60plusmn212 1185plusmn45 4

1905plusmn45 2355plusmn259 153plusmn519 1935plusmn960 114plusmn948 159plusmn173 6675plusmn309 1215plusmn45 1312plusmn0552 855plusmn193 6

153plusmn1024 1965plusmn135 1335plusmn1229 150plusmn34 735plusmn295 1365plusmn665 6181plusmn339 72plusmn244 907plusmn0951 5025plusmn143 8

135plusmn519 120plusmn346 11725plusmn1551 96plusmn874 525plusmn295 75plusmn173 153plusmn130 39plusmn212 3735plusmn0458 13125plusmn0552 12

Between normal and diseased

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (7) Urineserum concentrations ratios of ceftriaxone following repeated ntramuscular injection of 20 mg

ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats

(n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

229plusmn 163 1448plusmn0743 1885plusmn159 1125plusmn0484 533plusmn0260 1050plusmn358 175plusmn0380 4146plusmn116 ------- ------ Before

741plusmn0063 plusmn01553 58plusmn0242 plusmn0149390 422plusmn0206 683plusmn0106 245plusmn0092 667plusmn0306 0510plusmn0081 559plusmn0181 050

651plusmn0243 plusmn0065031 637plusmn0373 plusmn014431 565plusmn0243 plusmn0085300 360plusmn0303 plusmn0110312 279plusmn0121 534plusmn0248 1

836plusmn0150 plusmn00476322 862plusmn0180 plusmn010463 942plusmn0166 plusmn0130631 217plusmn0303 727plusmn0256 508plusmn0186 plusmn01680340 2

939plusmn0235 plusmn01580344 1006plusmn0710 plusmn00750310 999plusmn0542 plusmn02850344 565plusmn0223 641plusmn0241 48plusmn0164 plusmn014834 4

1005plusmn0418 2plusmn018813 1097plusmn0641 plusmn03979300 993plusmn0921 plusmn0252931 619plusmn0483 plusmn0362933 167plusmn0101 642plusmn0644 6

1091plusmn0649 plusmn075332339 1171plusmn0980 995plusmn0415 925plusmn0593 plusmn05593433 886plusmn0408 plusmn02510311 2055plusmn0311 plusmn02046310 8

2392plusmn129 plusmn032731396 1794plusmn0228 1222plusmn124 1418plusmn109 plusmn026733336 580plusmn0397 plusmn03951326 227plusmn0452 plusmn02740316 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (8) Creatinine clearance (mlmin10kgbwt) following repeated intramuscular injection of 20 mg ceftriaxonekgbwt

twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats (n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1115plusmn0703 2265plusmn167 481plusmn0409 672plusmn0817 669plusmn0672 1202plusmn0777 695plusmn0634 1724plusmn179 ----------- ------ Before

0703plusmn0091 147plusmn0305 0718plusmn0141 251plusmn0707 0547plusmn0055 0699plusmn0092 0802plusmn0099 103plusmn0106 295plusmn0124 0458plusmn0037 050

101plusmn0075 161plusmn0093 131plusmn0099 264plusmn0217 161plusmn0146 373plusmn0499 247plusmn0110 4755plusmn0582 214plusmn0234 103plusmn0166 1

157plusmn0198 387plusmn0340 173plusmn0501 267plusmn0217 187plusmn0563 287plusmn0499 451plusmn0223 972plusmn105 263plusmn0399 169plusmn0454 2

wwwwjppscom Vol 5 Issue 02 2016

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

184plusmn0095 346plusmn0444 173plusmn0501 436plusmn0599 383plusmn0299 682plusmn0584 328plusmn0253 119plusmn153 123plusmn0057 292plusmn0742 4

221plusmn0242 411plusmn0661 241plusmn0186 663plusmn0584 308plusmn0234 422plusmn0314 353plusmn0393 548plusmn0901 105plusmn0057 264plusmn0294 6

261plusmn0295 476plusmn0339 319plusmn0273 753plusmn0676 106plusmn0207 0773plusmn0049 228plusmn0175 456plusmn0340 206plusmn0160 404plusmn0419 8

310plusmn0218 409plusmn0434 3264plusmn0153 669plusmn0476 209plusmn0189 235plusmn0337 217plusmn0143 377plusmn0342 240plusmn0218 6055plusmn0176 12

Between normal and diseased

Plt 005 Plt001 Plt0001

Table (9) Ceftriaxone clearance (mlmin10kgbwt following repeated intramuscular injection of 20 mg ceftriaxone kgbwt

twice in normal and experimentally Salmonella typhimurim infected goats (n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1048plusmn121 0557plusmn684 895plusmn113 0547plusmn560 238plusmn0222 103plusmn 480 0668plusmn0157 0173plusmn216 -------- ----------- Before

156plusmn0251 43204plusmn3322 0936plusmn0162 43211plusmn3334 0473plusmn0037 43469plusmn43964 0300plusmn0028 43341plusmn080 0190plusmn0137 43400plusmn43642 050

166plusmn0079 43323plusmn3311 157plusmn0178 43419plusmn3301 137plusmn0115 43311plusmn33022 0883plusmn0054 43341plusmn 133 0616plusmn0153 43120plusmn3301 1

254plusmn0272 43361plusmn3391 222plusmn0093 4331plusmn3390 243plusmn0180 43209plusmn3309 183plusmn0149 43310plusmn2340 128plusmn0153 43312plusmn3390 2

181plusmn0136 43339plusmn3316 161plusmn0129 433plusmn3329 144plusmn0100 43412plusmn3349 0821plusmn0072 0063plusmn0977 0654plusmn0065 43400plusmn4306 4

160plusmn0177 43393plusmn336 152plusmn0200 43416plusmn331 135plusmn0118 4332plusmn3322 0897plusmn0052 43304plusmn3330 0212plusmn0022 43460plusmn43112 6

153plusmn0049 43291plusmn234 163plusmn0242 43346plusmn3300 0891plusmn0272 43306plusmn3310 108plusmn0071 43416plusmn04310 0229plusmn0046 43490plusmn43916 8

340plusmn0522 43214plusmn2341 249plusmn0150 43112plusmn3393 186plusmn0159 43320plusmn336 0773plusmn0094 43390plusmn 134 0264plusmn0043 43400plusmn 54369 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Table (10) Ceftriaxone clearancecreatinine clearance following repeated ntramuscular injection of 20 mg

ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats

(n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

0934plusmn0083 0305plusmn0013 183plusmn0116 0864plusmn0098 0358plusmn0018 0279plusmn0047 0099plusmn0020 0127plusmn0001 ------- ----------- Before

220plusmn0115 0819plusmn0044 131plusmn00414 0458plusmn0029 0876plusmn0063 126plusmn0068 0361plusmn0011 0813plusmn0031 0018plusmn0003 108plusmn0062 050

164plusmn0078 0818plusmn0029 118plusmn0068 0546plusmn0027 0858plusmn0052 0407plusmn0041 0331plusmn0009 0287plusmn0025 0324plusmn0011 0909plusmn0187 1

161plusmn0044 0488plusmn0005 232plusmn128 0329plusmn0027 169plusmn0464 0686plusmn0050 0409plusmn0020 0220plusmn0029 0512plusmn0077 266plusmn177 2

0933plusmn0024 0394plusmn0005 0948plusmn0062 0296plusmn0007 0381plusmn0027 0160plusmn0008 0235plusmn0014 0083plusmn0006 0528plusmn0028 0362plusmn0041 4

0726plusmn0018 0411plusmn0028 0639plusmn0066 0204plusmn0006 0446plusmn0034 0286plusmn0008 0238plusmn0019 0214plusmn0006 020plusmn0013 0382plusmn0028 6

0609plusmn0072 0425plusmn0036 0508plusmn0052 0192plusmn0009 0524plusmn0146 174plusmn0083 0477plusmn0015 0213plusmn00018 0109plusmn0185 0222plusmn0006 8

108plusmn0128 0496plusmn0012 0942plusmn0004 0265plusmn0030 0891plusmn0056 0706plusmn0103 0351plusmn0022 0354plusmn0018 0111plusmn0021 0098plusmn0018 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

DISCUSSION

In the present investigation intravenous injection of 20 mg ceftriaxonekgbwt in normal goats the drug showed high serum level

(92plusmn 0408 μgml) at 5 minutes post-injection then its concentration was decreased gradually till reached its minimum level (18

plusmn0816μgml) at 8hours post-injection

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In the present investigation the intravenous injection of 20 mg ceftriaxonekgbwt In normal

goats showed that the drug disposition best fitted a two-compartments- open model a

compartment of plasma and rapid equilibrating tissues and a deeper slower compartment

The obtained result is consistent with those reported for ceftriaxone in lactating goats[9]

lactating ewe[25]

domestic cat[15]

calves[26]

and patanwadi sheep[8]

Also this phenomenon is

in agreement with those reported for other cephalosporines as ceftazidime in a rabbit[27]

cefepime in dog and neonatal foals[28]

ewes[29]

ceftriaxone in goats[9]

cefipime in calves[30]

ceftiofur in cross-bred friesian cattle[31]

cefipime in calves[32]

ceftiofur in cows[33]

cefpirome

in cross-bred calves[3]

cefazidime in goats[35]

and cefquinome in sheep and goats[36]

cefipime

in chickens[37]

Ceftriaxone was distributed after intravenous injection with a distribution phase (α) equal to

656 per hour with a short distribution half ndash life [t05 (α)] equal to 0104 hour The shorter

distribution half-life of ceftriaxone in goats suggested the rapid distribution of the drug in

body tissue and fluid and that nearly similar to that recorded for ceftriaxone in lactating

goats(012 hour)[9]

for ceftriaxone in lactating ewes (0152 hour)[2]

and for ceftriaxone in

calves( 013hour)[26]

The rapid distribution of ceftriaxone in goats is supported by high rate constant of transfer of

the drug from central to peripheral compartment [K12 = 353 h-1

] as compared to the rate

constant of transfer of the drug from peripheral to central compartment [K21= 295 h-1

] This

value is nearly similar to those reported for cefotaxime in goats (K21=327 h-1

)[38]

On contrast

this value was higher than those recorded for ceftriaxone in lactating goats (K21=143 h-1

)[9]

in

lactating ewes (K21=125 h-1

)[25]

and in domestic cats (K21=154 h-1

)[15]

The apparent volume of distribution of ceftriaxone was (0355plusmn0004LKg) this value is

nearly similar to that recorded for cefaronide in sheep(039 LKg)[7]

cefotaxime in dog (048

lkg)[39]

in goat (051 lkg)

[40] for caphalexin in buffalo calves (041 Lkg)

[41] for cefipime in

ewes and calves (032 lkg) (043Lkg)[29]

and[30]

respectively For ceftriaxone in domestic

cats (057Lkg)[15]

in camel (032Lkg)[42]

On the other hand this result is differ than that

reported for cefotaxime in buffalo calves (117Lkg)[43]

High value of the volume of

distribution suggested extensive penetration power Drug with volume of distribution greater

than one literkilogram indicated wide distribution or extensive tissue binding or both[44]

The

apparent volume of distribution in the present study indicated moderate tissue penetrating

power This result agreed with[15]

for ceftriaxone in domestic cats

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Ceftriaxone is eliminated in the current study following a single intravenous injection with

elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the

data recorded for ceftizoxime in goats (624hours)[45]

On contrast this value was longer than

that reported for ceftriaxone in lactating ewe (175hours)[25]

for cefaronide in sheep (17

hours)[7]

For cephalexin in buffulo calves (216hours)[41]

for ceftriaxone in healthy horse

(162hours)[46]

also this value is longer than that recorded for ceftriaxone in lactating goats

(144hours)[9]

for cefipime in goats (186hours)[47]

The rate of total body clearance of ceftriaxone following a single intravenous injection is

0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]

On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating

goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)

(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]

respectively

The variation in total body clearance might be attributed to specific interspecies variation

handling of the drug method used healthy status of the animal[48]

The difference between values calculated for pharmacokinetic parameters may be attributed

to animal species the drug formulation employed the age the size or sex o l lf the animal

or even inter individual variation and also due to method of analysis of the drug[49]

Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the

drug reached its peak serum concentrations after one hour of injection with value

of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12

hours post-injection The reported peak serum concentrations neerly similar to that reported

for cephalexin in buffulo calves (457 microgml)[41]

These results is differed than those reported

for ceftriaxone in cross breed calves (188 microgml at 30 min[16]

in Kangro breed of goats

(Capra Hircus) (2640 microgml at 20 min[10][50]

found after intramuscular administration of

ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher

than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]

The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time

(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats

(4932 microgml[47]

The reported maximum serum concentration (Cmax) is higher than that

reported for ceftriaxone in lactating goats(236 microgml)[9]

in lactating ewes (1722 microgml[25]

in

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

goats (2151 microgml)[11]

for cefquinome in camels (123 microgml)[51]

for ceftriaxone in calves

(1534 microgml)[26]

in patanwadi sheep (1553 microgml)[8]

for cefpirome in cattle (101 microgml)[52]

And for ceftiofur in chickens (2594 μgml)[37]

On the other hand the result was lower than

that reported by[6]

who observed the maximum serum concentration (Cmax) of ceftriaxone in

human after ntramuscular administration was (805 microgml) also it was lower than that

reported for ceftriaxone in dog (11510 microgml)[53]

in domestic cats (5440 microgml)[15]

and for

ceftazoxime in goats (8878 microgml)[45]

The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating

ewes by[25]

On contrast it is longer than those reported for ceftriaxone in dogs

(129hours)[53]

for ceftriaxone in lactating goats (07hours)[9]

also the result was longer than

that reported for ceftriaxone in domestic cats (033hours)[15]

in buffulo calves (05 hours)[13]

and for cefpirome in cattle (075hours)[52]

The reported [tmax] is shorter than those reported

for cefquinome in camels (425hours)[51]

in sheep and goats (261 and 262 hours)[36]

and for

ceftiofur in chickens (251 hours)[37]

The elimination half life [t05(β)]

following a single intramuscular administration was 1804 hours This value is nearly agreed

with that recorded for cefquinomein camels (1024hours)[52]

On contrast this result is longer

than that reported for cephalexin in buffalo calves (243hours)[41]

for ceftriaxone in lactating

ewes (177hours)[25]

in buffalo calves (438hours)[13]

in goats (203 hours)[11]

and for

cefipime in goats (165 hours)[47]

The rate of total body clearance of ceftriaxone following a single intramuscular injection is

0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves

(401Lkgh)[13]

in goats (304 Lkgh)[11]

and in sheep (222 Lkgh)[8]

Bioavailability is the fraction of the drug administered by non vascular rout that gains

accesses to the systemic circulation The obtained result revealed that the calculated systemic

bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves

(61)[54]

It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]

On the other

hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]

for ceftriaxone in goats (59)[11]

in calves (47)[55]

On contrast this value is lower than

those reported for cefotaxime in two cats 982 and 93)[57]

for cephradine in goats

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

(739)[58]

for ceftazidime in a rabbit (966)[27]

for ceftriaxone in lactating goats (85)[9]

in lactating ewes (836)[25]

in domestic cats 8572[15]

for cefipime in goats 8645[47]

for ceftriaxone in buffulo calves 702[13]

and for ceftiofur in chickens 8890[37]

Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium

infected goats twics dialy for five days revealed that the drug could be detected in a

therapeutic level for 12hours following repeated intramuscular administrations and exceeded

the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]

The relative higher serum concentrations of ceftriaxone after the last dose compared to the

first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12

hours intervals for five consecutive days These observations agreed with data reported by[36]

on comparing the data of serum levels of repeated intramuscular injections with first

intramuscular injection it was revealed that repeated intramuscular injections of cefquinome

have cumulative effect in both species sheep and goats

The obtained result is inconsistent with that reported by[56]

who found thatwhen cefotaxime

was administered repetitively in patients the ratio of maximal serum levels after the last dose

to those after the first dose demonstrated minimal accumulation of intact drug and by[60]

who

found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in

buffalo calves

The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium

infected goats are significantly lower than those in normal goats following repeated

intramuscular injection These lower blood concentrations in Salmonella typhimurium

infected goats might be attributed to the higher penetrating power of ceftriaxone to the

diseased tissues[48]

This phenomenon is similar to data recorded by[61]

who suggested that

Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of

ceftriaxone These alterations might be due to fever and inflammation induced by

infections[59]

proved that the serum concentrations of cephradine following intramuscular

administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after

each intramuscular dose with a lower significant values recorded in Escherichia-coli infected

goats than in normal goatsAlso similer to that reported by[62]

who observed that the

maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

in comparison to normal sheepOn contrast[43]

reported that peak plasma level of cefotaxime

in febrile buffalo calves was higher than healthy buffalo calves

In this study the total body clearance (CLtot) in normal goats are significantly lower than in

Salmonella typhimurium infected goats This result supported by[61]

and[63]

fever and

inflammation are cardinal features in bacterial infection which may in turn caused an

increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all

these could lead to increased in the rate at which the drug was delivered to both organs which

were important sites of drug excretion This might somewhat explain the increase in the total

body clearance in infected goats This result is differ than that reported by[64]

who observed

that the clearance of ceftriaxone was significantly reduced in infected mice than in non

infected animals

The highest concentrations of ceftriaxone in milk are recorded 4 hours after each

intramuscular injection with a significant lower value in Salmonella typhimurium infected

goats than in normal goats This might be attributed to accumulation of drug in the inflammed

tissues[48]

This result is similar to those reported by[6559]

who found that milk concentrations

of gentamicin and cephradine were significantly lower in infected goats and cattle than in

normal ones respectively

The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the

non-ionic passive diffusion principle[66]

reported that most drug cross-lipid membranes by

passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly

influenced by the physicochemical properties of the drug[6768]

Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum

ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the

physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]

Milk

contains substantially more lipid and less protein than serum and is slightly more acidic

Therefore drugs which tend to concentrated in milk are weak bases with low serum protein

binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide

and aminothiazole also possesses an hydroxytriazinone group as new and additional

ionization center[70]

these compounds are sufficiently lipid- soluble to be able to penetrate

tissues

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

The dose of ceftriaxone used in the present study induced therapeutically concentrations in

milk These concentrations suggested that ceftriaxone would be efficacious in treatment of

mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily

for 3-5 days

The study showed that the urine concentrations of ceftriaxone are greater than the concurrent

serum concentrations following intramuscular injection This observation is similar to those

reported in cows after cephapirin administrations[71]

In the present study urine concentrations of ceftriaxone increased with the repetition of

dosing This observation supported by[72]

after repeated intramuscular administrations of

ceftriaxone in healthy volunteeres

The mean peak urine concentrations of ceftriaxone were reached 2 hours after each

intramuscular injection The lower urine ceftriaxone concentrations in Salmonella

typhimurium infected goats than in normal goats might be attributed to the accumulation of

the drug in the inflamed tissues[48]

The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower

ratio in Salmonella typhimurium infected goats than in normal goats at different time of

sampling This indicates that glomerular filteration seemed to be the main pathway of

ceftriaxone elimination This observation supported by[59]

who found that the ratio between

cephradine clearance from blood of goats to creatinine clearance showed a marked decrease

in Escherichia-coli infected goats than in normal goats This indicated that glomerular

filteration seemed to be the main pathway of cephradine elimination with a limited rate of

tubular reabsorption

CONCLUSION

The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value

referred a better absorption of ceftriaxone from its site of intramuscular administration The

high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular

administrations suggested that ceftriaxone could be used for treatment of mastitis caused by

Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats

The high concentrations of ceftriaxone in urine after repeated intramuscular administrations

suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections

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caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in

goats

REFERANCES

1 Neu HC Merpol NJ and Fukp (1981) Antibacterial activity of ceftriaxone

abetalactamase stable cephalosporines Antimicrobial agents and chemotherapy 19

414-423

2 Richard DM Heel RC Brogden RN Speight TM Avery GS (1984) Ceftriaxone a

review of its antibacterial activity pharmacological properties and therapeutic uses

Drugs 27 469-527

3 Brogden RN and Ward A (1988) Ceftriaxone a reappraisal of its antibacterial activity

and pharmacokinetic properties and an update on its therapeutic use with particular

reference to once-daily administration Drugs 35 604-645

4 Waxman DJ and Strominger JL (1983) Penicillin-binding proteins and the

mechanism of action of beta-lactam antibiotics Annu Rev Biochem 52(1) 825-869

5 Christ W (1991) properties of cephalosporines Infestion 19 244-252

6 Goonetilleke AK Dev D Aziz I Hughes C Smith MJ Basran GS (1996) A

comparative analysis of pharmacokinetics of ceftriaxone in serum and pleural fluid in

humans a study of once daily administration by intramuscular intravenous routes J

Antimicrob Chemother Dec 38(6) 969-76

7 Guerrini VH Filippich LJ Cao G R English PB Bourne DW (1985)

Pharmacokinetics of cefaronide ceftriaxone and cefperazone in sheep J Vet Pharmacol

Ther 8(2) 120-7

8 Swati Tiwari S Patel UD Bhavsar SK and Thaker AM (2010) Pharmacokinetics

and Bioavailability of Ceftriaxone in Patanwadi Sheep Online veterinary journal 5(2)

9 Ismail MM (2005) Pharmacokinetics urinary and mammary excretion of ceftriaxone in

lactating goats J Vet Med A Physiol Pathol Clin Med Sep 52(7) 354-8

10 Rajinder R prawez S Srivastiva AS (2005) Pharmacokinetics and dosage regimen of

ceftriaxone following its single ntramuscular adminsteration in kagani breed of goats

(Capra Hircus) Journal of reaserch 4(2) 91-93

11 Tiwari S Swati Bhavsar SK Patel UD and Thaker AM (2009) Disposition of

Ceftriaxone in Goats (Capra hircus) Online veterinary journal 4(2)

12 Dardi MS Sharma SK and Srivastava AK (2004) Pharmacokinetics and Dosage

regimen of ceftriaxone in buffalo calves Vet Res Commun 28 331-338

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Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (7) Urineserum concentrations ratios of ceftriaxone following repeated ntramuscular injection of 20 mg

ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats

(n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

229plusmn 163 1448plusmn0743 1885plusmn159 1125plusmn0484 533plusmn0260 1050plusmn358 175plusmn0380 4146plusmn116 ------- ------ Before

741plusmn0063 plusmn01553 58plusmn0242 plusmn0149390 422plusmn0206 683plusmn0106 245plusmn0092 667plusmn0306 0510plusmn0081 559plusmn0181 050

651plusmn0243 plusmn0065031 637plusmn0373 plusmn014431 565plusmn0243 plusmn0085300 360plusmn0303 plusmn0110312 279plusmn0121 534plusmn0248 1

836plusmn0150 plusmn00476322 862plusmn0180 plusmn010463 942plusmn0166 plusmn0130631 217plusmn0303 727plusmn0256 508plusmn0186 plusmn01680340 2

939plusmn0235 plusmn01580344 1006plusmn0710 plusmn00750310 999plusmn0542 plusmn02850344 565plusmn0223 641plusmn0241 48plusmn0164 plusmn014834 4

1005plusmn0418 2plusmn018813 1097plusmn0641 plusmn03979300 993plusmn0921 plusmn0252931 619plusmn0483 plusmn0362933 167plusmn0101 642plusmn0644 6

1091plusmn0649 plusmn075332339 1171plusmn0980 995plusmn0415 925plusmn0593 plusmn05593433 886plusmn0408 plusmn02510311 2055plusmn0311 plusmn02046310 8

2392plusmn129 plusmn032731396 1794plusmn0228 1222plusmn124 1418plusmn109 plusmn026733336 580plusmn0397 plusmn03951326 227plusmn0452 plusmn02740316 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

Table (8) Creatinine clearance (mlmin10kgbwt) following repeated intramuscular injection of 20 mg ceftriaxonekgbwt

twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats (n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1115plusmn0703 2265plusmn167 481plusmn0409 672plusmn0817 669plusmn0672 1202plusmn0777 695plusmn0634 1724plusmn179 ----------- ------ Before

0703plusmn0091 147plusmn0305 0718plusmn0141 251plusmn0707 0547plusmn0055 0699plusmn0092 0802plusmn0099 103plusmn0106 295plusmn0124 0458plusmn0037 050

101plusmn0075 161plusmn0093 131plusmn0099 264plusmn0217 161plusmn0146 373plusmn0499 247plusmn0110 4755plusmn0582 214plusmn0234 103plusmn0166 1

157plusmn0198 387plusmn0340 173plusmn0501 267plusmn0217 187plusmn0563 287plusmn0499 451plusmn0223 972plusmn105 263plusmn0399 169plusmn0454 2

wwwwjppscom Vol 5 Issue 02 2016

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

184plusmn0095 346plusmn0444 173plusmn0501 436plusmn0599 383plusmn0299 682plusmn0584 328plusmn0253 119plusmn153 123plusmn0057 292plusmn0742 4

221plusmn0242 411plusmn0661 241plusmn0186 663plusmn0584 308plusmn0234 422plusmn0314 353plusmn0393 548plusmn0901 105plusmn0057 264plusmn0294 6

261plusmn0295 476plusmn0339 319plusmn0273 753plusmn0676 106plusmn0207 0773plusmn0049 228plusmn0175 456plusmn0340 206plusmn0160 404plusmn0419 8

310plusmn0218 409plusmn0434 3264plusmn0153 669plusmn0476 209plusmn0189 235plusmn0337 217plusmn0143 377plusmn0342 240plusmn0218 6055plusmn0176 12

Between normal and diseased

Plt 005 Plt001 Plt0001

Table (9) Ceftriaxone clearance (mlmin10kgbwt following repeated intramuscular injection of 20 mg ceftriaxone kgbwt

twice in normal and experimentally Salmonella typhimurim infected goats (n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1048plusmn121 0557plusmn684 895plusmn113 0547plusmn560 238plusmn0222 103plusmn 480 0668plusmn0157 0173plusmn216 -------- ----------- Before

156plusmn0251 43204plusmn3322 0936plusmn0162 43211plusmn3334 0473plusmn0037 43469plusmn43964 0300plusmn0028 43341plusmn080 0190plusmn0137 43400plusmn43642 050

166plusmn0079 43323plusmn3311 157plusmn0178 43419plusmn3301 137plusmn0115 43311plusmn33022 0883plusmn0054 43341plusmn 133 0616plusmn0153 43120plusmn3301 1

254plusmn0272 43361plusmn3391 222plusmn0093 4331plusmn3390 243plusmn0180 43209plusmn3309 183plusmn0149 43310plusmn2340 128plusmn0153 43312plusmn3390 2

181plusmn0136 43339plusmn3316 161plusmn0129 433plusmn3329 144plusmn0100 43412plusmn3349 0821plusmn0072 0063plusmn0977 0654plusmn0065 43400plusmn4306 4

160plusmn0177 43393plusmn336 152plusmn0200 43416plusmn331 135plusmn0118 4332plusmn3322 0897plusmn0052 43304plusmn3330 0212plusmn0022 43460plusmn43112 6

153plusmn0049 43291plusmn234 163plusmn0242 43346plusmn3300 0891plusmn0272 43306plusmn3310 108plusmn0071 43416plusmn04310 0229plusmn0046 43490plusmn43916 8

340plusmn0522 43214plusmn2341 249plusmn0150 43112plusmn3393 186plusmn0159 43320plusmn336 0773plusmn0094 43390plusmn 134 0264plusmn0043 43400plusmn 54369 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Table (10) Ceftriaxone clearancecreatinine clearance following repeated ntramuscular injection of 20 mg

ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats

(n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

0934plusmn0083 0305plusmn0013 183plusmn0116 0864plusmn0098 0358plusmn0018 0279plusmn0047 0099plusmn0020 0127plusmn0001 ------- ----------- Before

220plusmn0115 0819plusmn0044 131plusmn00414 0458plusmn0029 0876plusmn0063 126plusmn0068 0361plusmn0011 0813plusmn0031 0018plusmn0003 108plusmn0062 050

164plusmn0078 0818plusmn0029 118plusmn0068 0546plusmn0027 0858plusmn0052 0407plusmn0041 0331plusmn0009 0287plusmn0025 0324plusmn0011 0909plusmn0187 1

161plusmn0044 0488plusmn0005 232plusmn128 0329plusmn0027 169plusmn0464 0686plusmn0050 0409plusmn0020 0220plusmn0029 0512plusmn0077 266plusmn177 2

0933plusmn0024 0394plusmn0005 0948plusmn0062 0296plusmn0007 0381plusmn0027 0160plusmn0008 0235plusmn0014 0083plusmn0006 0528plusmn0028 0362plusmn0041 4

0726plusmn0018 0411plusmn0028 0639plusmn0066 0204plusmn0006 0446plusmn0034 0286plusmn0008 0238plusmn0019 0214plusmn0006 020plusmn0013 0382plusmn0028 6

0609plusmn0072 0425plusmn0036 0508plusmn0052 0192plusmn0009 0524plusmn0146 174plusmn0083 0477plusmn0015 0213plusmn00018 0109plusmn0185 0222plusmn0006 8

108plusmn0128 0496plusmn0012 0942plusmn0004 0265plusmn0030 0891plusmn0056 0706plusmn0103 0351plusmn0022 0354plusmn0018 0111plusmn0021 0098plusmn0018 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

DISCUSSION

In the present investigation intravenous injection of 20 mg ceftriaxonekgbwt in normal goats the drug showed high serum level

(92plusmn 0408 μgml) at 5 minutes post-injection then its concentration was decreased gradually till reached its minimum level (18

plusmn0816μgml) at 8hours post-injection

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

In the present investigation the intravenous injection of 20 mg ceftriaxonekgbwt In normal

goats showed that the drug disposition best fitted a two-compartments- open model a

compartment of plasma and rapid equilibrating tissues and a deeper slower compartment

The obtained result is consistent with those reported for ceftriaxone in lactating goats[9]

lactating ewe[25]

domestic cat[15]

calves[26]

and patanwadi sheep[8]

Also this phenomenon is

in agreement with those reported for other cephalosporines as ceftazidime in a rabbit[27]

cefepime in dog and neonatal foals[28]

ewes[29]

ceftriaxone in goats[9]

cefipime in calves[30]

ceftiofur in cross-bred friesian cattle[31]

cefipime in calves[32]

ceftiofur in cows[33]

cefpirome

in cross-bred calves[3]

cefazidime in goats[35]

and cefquinome in sheep and goats[36]

cefipime

in chickens[37]

Ceftriaxone was distributed after intravenous injection with a distribution phase (α) equal to

656 per hour with a short distribution half ndash life [t05 (α)] equal to 0104 hour The shorter

distribution half-life of ceftriaxone in goats suggested the rapid distribution of the drug in

body tissue and fluid and that nearly similar to that recorded for ceftriaxone in lactating

goats(012 hour)[9]

for ceftriaxone in lactating ewes (0152 hour)[2]

and for ceftriaxone in

calves( 013hour)[26]

The rapid distribution of ceftriaxone in goats is supported by high rate constant of transfer of

the drug from central to peripheral compartment [K12 = 353 h-1

] as compared to the rate

constant of transfer of the drug from peripheral to central compartment [K21= 295 h-1

] This

value is nearly similar to those reported for cefotaxime in goats (K21=327 h-1

)[38]

On contrast

this value was higher than those recorded for ceftriaxone in lactating goats (K21=143 h-1

)[9]

in

lactating ewes (K21=125 h-1

)[25]

and in domestic cats (K21=154 h-1

)[15]

The apparent volume of distribution of ceftriaxone was (0355plusmn0004LKg) this value is

nearly similar to that recorded for cefaronide in sheep(039 LKg)[7]

cefotaxime in dog (048

lkg)[39]

in goat (051 lkg)

[40] for caphalexin in buffalo calves (041 Lkg)

[41] for cefipime in

ewes and calves (032 lkg) (043Lkg)[29]

and[30]

respectively For ceftriaxone in domestic

cats (057Lkg)[15]

in camel (032Lkg)[42]

On the other hand this result is differ than that

reported for cefotaxime in buffalo calves (117Lkg)[43]

High value of the volume of

distribution suggested extensive penetration power Drug with volume of distribution greater

than one literkilogram indicated wide distribution or extensive tissue binding or both[44]

The

apparent volume of distribution in the present study indicated moderate tissue penetrating

power This result agreed with[15]

for ceftriaxone in domestic cats

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

Ceftriaxone is eliminated in the current study following a single intravenous injection with

elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the

data recorded for ceftizoxime in goats (624hours)[45]

On contrast this value was longer than

that reported for ceftriaxone in lactating ewe (175hours)[25]

for cefaronide in sheep (17

hours)[7]

For cephalexin in buffulo calves (216hours)[41]

for ceftriaxone in healthy horse

(162hours)[46]

also this value is longer than that recorded for ceftriaxone in lactating goats

(144hours)[9]

for cefipime in goats (186hours)[47]

The rate of total body clearance of ceftriaxone following a single intravenous injection is

0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]

On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating

goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)

(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]

respectively

The variation in total body clearance might be attributed to specific interspecies variation

handling of the drug method used healthy status of the animal[48]

The difference between values calculated for pharmacokinetic parameters may be attributed

to animal species the drug formulation employed the age the size or sex o l lf the animal

or even inter individual variation and also due to method of analysis of the drug[49]

Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the

drug reached its peak serum concentrations after one hour of injection with value

of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12

hours post-injection The reported peak serum concentrations neerly similar to that reported

for cephalexin in buffulo calves (457 microgml)[41]

These results is differed than those reported

for ceftriaxone in cross breed calves (188 microgml at 30 min[16]

in Kangro breed of goats

(Capra Hircus) (2640 microgml at 20 min[10][50]

found after intramuscular administration of

ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher

than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]

The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time

(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats

(4932 microgml[47]

The reported maximum serum concentration (Cmax) is higher than that

reported for ceftriaxone in lactating goats(236 microgml)[9]

in lactating ewes (1722 microgml[25]

in

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

goats (2151 microgml)[11]

for cefquinome in camels (123 microgml)[51]

for ceftriaxone in calves

(1534 microgml)[26]

in patanwadi sheep (1553 microgml)[8]

for cefpirome in cattle (101 microgml)[52]

And for ceftiofur in chickens (2594 μgml)[37]

On the other hand the result was lower than

that reported by[6]

who observed the maximum serum concentration (Cmax) of ceftriaxone in

human after ntramuscular administration was (805 microgml) also it was lower than that

reported for ceftriaxone in dog (11510 microgml)[53]

in domestic cats (5440 microgml)[15]

and for

ceftazoxime in goats (8878 microgml)[45]

The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating

ewes by[25]

On contrast it is longer than those reported for ceftriaxone in dogs

(129hours)[53]

for ceftriaxone in lactating goats (07hours)[9]

also the result was longer than

that reported for ceftriaxone in domestic cats (033hours)[15]

in buffulo calves (05 hours)[13]

and for cefpirome in cattle (075hours)[52]

The reported [tmax] is shorter than those reported

for cefquinome in camels (425hours)[51]

in sheep and goats (261 and 262 hours)[36]

and for

ceftiofur in chickens (251 hours)[37]

The elimination half life [t05(β)]

following a single intramuscular administration was 1804 hours This value is nearly agreed

with that recorded for cefquinomein camels (1024hours)[52]

On contrast this result is longer

than that reported for cephalexin in buffalo calves (243hours)[41]

for ceftriaxone in lactating

ewes (177hours)[25]

in buffalo calves (438hours)[13]

in goats (203 hours)[11]

and for

cefipime in goats (165 hours)[47]

The rate of total body clearance of ceftriaxone following a single intramuscular injection is

0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves

(401Lkgh)[13]

in goats (304 Lkgh)[11]

and in sheep (222 Lkgh)[8]

Bioavailability is the fraction of the drug administered by non vascular rout that gains

accesses to the systemic circulation The obtained result revealed that the calculated systemic

bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves

(61)[54]

It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]

On the other

hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]

for ceftriaxone in goats (59)[11]

in calves (47)[55]

On contrast this value is lower than

those reported for cefotaxime in two cats 982 and 93)[57]

for cephradine in goats

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

(739)[58]

for ceftazidime in a rabbit (966)[27]

for ceftriaxone in lactating goats (85)[9]

in lactating ewes (836)[25]

in domestic cats 8572[15]

for cefipime in goats 8645[47]

for ceftriaxone in buffulo calves 702[13]

and for ceftiofur in chickens 8890[37]

Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium

infected goats twics dialy for five days revealed that the drug could be detected in a

therapeutic level for 12hours following repeated intramuscular administrations and exceeded

the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]

The relative higher serum concentrations of ceftriaxone after the last dose compared to the

first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12

hours intervals for five consecutive days These observations agreed with data reported by[36]

on comparing the data of serum levels of repeated intramuscular injections with first

intramuscular injection it was revealed that repeated intramuscular injections of cefquinome

have cumulative effect in both species sheep and goats

The obtained result is inconsistent with that reported by[56]

who found thatwhen cefotaxime

was administered repetitively in patients the ratio of maximal serum levels after the last dose

to those after the first dose demonstrated minimal accumulation of intact drug and by[60]

who

found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in

buffalo calves

The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium

infected goats are significantly lower than those in normal goats following repeated

intramuscular injection These lower blood concentrations in Salmonella typhimurium

infected goats might be attributed to the higher penetrating power of ceftriaxone to the

diseased tissues[48]

This phenomenon is similar to data recorded by[61]

who suggested that

Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of

ceftriaxone These alterations might be due to fever and inflammation induced by

infections[59]

proved that the serum concentrations of cephradine following intramuscular

administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after

each intramuscular dose with a lower significant values recorded in Escherichia-coli infected

goats than in normal goatsAlso similer to that reported by[62]

who observed that the

maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep

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1451

Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

in comparison to normal sheepOn contrast[43]

reported that peak plasma level of cefotaxime

in febrile buffalo calves was higher than healthy buffalo calves

In this study the total body clearance (CLtot) in normal goats are significantly lower than in

Salmonella typhimurium infected goats This result supported by[61]

and[63]

fever and

inflammation are cardinal features in bacterial infection which may in turn caused an

increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all

these could lead to increased in the rate at which the drug was delivered to both organs which

were important sites of drug excretion This might somewhat explain the increase in the total

body clearance in infected goats This result is differ than that reported by[64]

who observed

that the clearance of ceftriaxone was significantly reduced in infected mice than in non

infected animals

The highest concentrations of ceftriaxone in milk are recorded 4 hours after each

intramuscular injection with a significant lower value in Salmonella typhimurium infected

goats than in normal goats This might be attributed to accumulation of drug in the inflammed

tissues[48]

This result is similar to those reported by[6559]

who found that milk concentrations

of gentamicin and cephradine were significantly lower in infected goats and cattle than in

normal ones respectively

The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the

non-ionic passive diffusion principle[66]

reported that most drug cross-lipid membranes by

passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly

influenced by the physicochemical properties of the drug[6768]

Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum

ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the

physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]

Milk

contains substantially more lipid and less protein than serum and is slightly more acidic

Therefore drugs which tend to concentrated in milk are weak bases with low serum protein

binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide

and aminothiazole also possesses an hydroxytriazinone group as new and additional

ionization center[70]

these compounds are sufficiently lipid- soluble to be able to penetrate

tissues

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

The dose of ceftriaxone used in the present study induced therapeutically concentrations in

milk These concentrations suggested that ceftriaxone would be efficacious in treatment of

mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily

for 3-5 days

The study showed that the urine concentrations of ceftriaxone are greater than the concurrent

serum concentrations following intramuscular injection This observation is similar to those

reported in cows after cephapirin administrations[71]

In the present study urine concentrations of ceftriaxone increased with the repetition of

dosing This observation supported by[72]

after repeated intramuscular administrations of

ceftriaxone in healthy volunteeres

The mean peak urine concentrations of ceftriaxone were reached 2 hours after each

intramuscular injection The lower urine ceftriaxone concentrations in Salmonella

typhimurium infected goats than in normal goats might be attributed to the accumulation of

the drug in the inflamed tissues[48]

The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower

ratio in Salmonella typhimurium infected goats than in normal goats at different time of

sampling This indicates that glomerular filteration seemed to be the main pathway of

ceftriaxone elimination This observation supported by[59]

who found that the ratio between

cephradine clearance from blood of goats to creatinine clearance showed a marked decrease

in Escherichia-coli infected goats than in normal goats This indicated that glomerular

filteration seemed to be the main pathway of cephradine elimination with a limited rate of

tubular reabsorption

CONCLUSION

The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value

referred a better absorption of ceftriaxone from its site of intramuscular administration The

high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular

administrations suggested that ceftriaxone could be used for treatment of mastitis caused by

Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats

The high concentrations of ceftriaxone in urine after repeated intramuscular administrations

suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in

goats

REFERANCES

1 Neu HC Merpol NJ and Fukp (1981) Antibacterial activity of ceftriaxone

abetalactamase stable cephalosporines Antimicrobial agents and chemotherapy 19

414-423

2 Richard DM Heel RC Brogden RN Speight TM Avery GS (1984) Ceftriaxone a

review of its antibacterial activity pharmacological properties and therapeutic uses

Drugs 27 469-527

3 Brogden RN and Ward A (1988) Ceftriaxone a reappraisal of its antibacterial activity

and pharmacokinetic properties and an update on its therapeutic use with particular

reference to once-daily administration Drugs 35 604-645

4 Waxman DJ and Strominger JL (1983) Penicillin-binding proteins and the

mechanism of action of beta-lactam antibiotics Annu Rev Biochem 52(1) 825-869

5 Christ W (1991) properties of cephalosporines Infestion 19 244-252

6 Goonetilleke AK Dev D Aziz I Hughes C Smith MJ Basran GS (1996) A

comparative analysis of pharmacokinetics of ceftriaxone in serum and pleural fluid in

humans a study of once daily administration by intramuscular intravenous routes J

Antimicrob Chemother Dec 38(6) 969-76

7 Guerrini VH Filippich LJ Cao G R English PB Bourne DW (1985)

Pharmacokinetics of cefaronide ceftriaxone and cefperazone in sheep J Vet Pharmacol

Ther 8(2) 120-7

8 Swati Tiwari S Patel UD Bhavsar SK and Thaker AM (2010) Pharmacokinetics

and Bioavailability of Ceftriaxone in Patanwadi Sheep Online veterinary journal 5(2)

9 Ismail MM (2005) Pharmacokinetics urinary and mammary excretion of ceftriaxone in

lactating goats J Vet Med A Physiol Pathol Clin Med Sep 52(7) 354-8

10 Rajinder R prawez S Srivastiva AS (2005) Pharmacokinetics and dosage regimen of

ceftriaxone following its single ntramuscular adminsteration in kagani breed of goats

(Capra Hircus) Journal of reaserch 4(2) 91-93

11 Tiwari S Swati Bhavsar SK Patel UD and Thaker AM (2009) Disposition of

Ceftriaxone in Goats (Capra hircus) Online veterinary journal 4(2)

12 Dardi MS Sharma SK and Srivastava AK (2004) Pharmacokinetics and Dosage

regimen of ceftriaxone in buffalo calves Vet Res Commun 28 331-338

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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

184plusmn0095 346plusmn0444 173plusmn0501 436plusmn0599 383plusmn0299 682plusmn0584 328plusmn0253 119plusmn153 123plusmn0057 292plusmn0742 4

221plusmn0242 411plusmn0661 241plusmn0186 663plusmn0584 308plusmn0234 422plusmn0314 353plusmn0393 548plusmn0901 105plusmn0057 264plusmn0294 6

261plusmn0295 476plusmn0339 319plusmn0273 753plusmn0676 106plusmn0207 0773plusmn0049 228plusmn0175 456plusmn0340 206plusmn0160 404plusmn0419 8

310plusmn0218 409plusmn0434 3264plusmn0153 669plusmn0476 209plusmn0189 235plusmn0337 217plusmn0143 377plusmn0342 240plusmn0218 6055plusmn0176 12

Between normal and diseased

Plt 005 Plt001 Plt0001

Table (9) Ceftriaxone clearance (mlmin10kgbwt following repeated intramuscular injection of 20 mg ceftriaxone kgbwt

twice in normal and experimentally Salmonella typhimurim infected goats (n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

1048plusmn121 0557plusmn684 895plusmn113 0547plusmn560 238plusmn0222 103plusmn 480 0668plusmn0157 0173plusmn216 -------- ----------- Before

156plusmn0251 43204plusmn3322 0936plusmn0162 43211plusmn3334 0473plusmn0037 43469plusmn43964 0300plusmn0028 43341plusmn080 0190plusmn0137 43400plusmn43642 050

166plusmn0079 43323plusmn3311 157plusmn0178 43419plusmn3301 137plusmn0115 43311plusmn33022 0883plusmn0054 43341plusmn 133 0616plusmn0153 43120plusmn3301 1

254plusmn0272 43361plusmn3391 222plusmn0093 4331plusmn3390 243plusmn0180 43209plusmn3309 183plusmn0149 43310plusmn2340 128plusmn0153 43312plusmn3390 2

181plusmn0136 43339plusmn3316 161plusmn0129 433plusmn3329 144plusmn0100 43412plusmn3349 0821plusmn0072 0063plusmn0977 0654plusmn0065 43400plusmn4306 4

160plusmn0177 43393plusmn336 152plusmn0200 43416plusmn331 135plusmn0118 4332plusmn3322 0897plusmn0052 43304plusmn3330 0212plusmn0022 43460plusmn43112 6

153plusmn0049 43291plusmn234 163plusmn0242 43346plusmn3300 0891plusmn0272 43306plusmn3310 108plusmn0071 43416plusmn04310 0229plusmn0046 43490plusmn43916 8

340plusmn0522 43214plusmn2341 249plusmn0150 43112plusmn3393 186plusmn0159 43320plusmn336 0773plusmn0094 43390plusmn 134 0264plusmn0043 43400plusmn 54369 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

wwwwjppscom Vol 5 Issue 02 2016

1446

Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Table (10) Ceftriaxone clearancecreatinine clearance following repeated ntramuscular injection of 20 mg

ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats

(n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

0934plusmn0083 0305plusmn0013 183plusmn0116 0864plusmn0098 0358plusmn0018 0279plusmn0047 0099plusmn0020 0127plusmn0001 ------- ----------- Before

220plusmn0115 0819plusmn0044 131plusmn00414 0458plusmn0029 0876plusmn0063 126plusmn0068 0361plusmn0011 0813plusmn0031 0018plusmn0003 108plusmn0062 050

164plusmn0078 0818plusmn0029 118plusmn0068 0546plusmn0027 0858plusmn0052 0407plusmn0041 0331plusmn0009 0287plusmn0025 0324plusmn0011 0909plusmn0187 1

161plusmn0044 0488plusmn0005 232plusmn128 0329plusmn0027 169plusmn0464 0686plusmn0050 0409plusmn0020 0220plusmn0029 0512plusmn0077 266plusmn177 2

0933plusmn0024 0394plusmn0005 0948plusmn0062 0296plusmn0007 0381plusmn0027 0160plusmn0008 0235plusmn0014 0083plusmn0006 0528plusmn0028 0362plusmn0041 4

0726plusmn0018 0411plusmn0028 0639plusmn0066 0204plusmn0006 0446plusmn0034 0286plusmn0008 0238plusmn0019 0214plusmn0006 020plusmn0013 0382plusmn0028 6

0609plusmn0072 0425plusmn0036 0508plusmn0052 0192plusmn0009 0524plusmn0146 174plusmn0083 0477plusmn0015 0213plusmn00018 0109plusmn0185 0222plusmn0006 8

108plusmn0128 0496plusmn0012 0942plusmn0004 0265plusmn0030 0891plusmn0056 0706plusmn0103 0351plusmn0022 0354plusmn0018 0111plusmn0021 0098plusmn0018 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

DISCUSSION

In the present investigation intravenous injection of 20 mg ceftriaxonekgbwt in normal goats the drug showed high serum level

(92plusmn 0408 μgml) at 5 minutes post-injection then its concentration was decreased gradually till reached its minimum level (18

plusmn0816μgml) at 8hours post-injection

wwwwjppscom Vol 5 Issue 01 2016

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

In the present investigation the intravenous injection of 20 mg ceftriaxonekgbwt In normal

goats showed that the drug disposition best fitted a two-compartments- open model a

compartment of plasma and rapid equilibrating tissues and a deeper slower compartment

The obtained result is consistent with those reported for ceftriaxone in lactating goats[9]

lactating ewe[25]

domestic cat[15]

calves[26]

and patanwadi sheep[8]

Also this phenomenon is

in agreement with those reported for other cephalosporines as ceftazidime in a rabbit[27]

cefepime in dog and neonatal foals[28]

ewes[29]

ceftriaxone in goats[9]

cefipime in calves[30]

ceftiofur in cross-bred friesian cattle[31]

cefipime in calves[32]

ceftiofur in cows[33]

cefpirome

in cross-bred calves[3]

cefazidime in goats[35]

and cefquinome in sheep and goats[36]

cefipime

in chickens[37]

Ceftriaxone was distributed after intravenous injection with a distribution phase (α) equal to

656 per hour with a short distribution half ndash life [t05 (α)] equal to 0104 hour The shorter

distribution half-life of ceftriaxone in goats suggested the rapid distribution of the drug in

body tissue and fluid and that nearly similar to that recorded for ceftriaxone in lactating

goats(012 hour)[9]

for ceftriaxone in lactating ewes (0152 hour)[2]

and for ceftriaxone in

calves( 013hour)[26]

The rapid distribution of ceftriaxone in goats is supported by high rate constant of transfer of

the drug from central to peripheral compartment [K12 = 353 h-1

] as compared to the rate

constant of transfer of the drug from peripheral to central compartment [K21= 295 h-1

] This

value is nearly similar to those reported for cefotaxime in goats (K21=327 h-1

)[38]

On contrast

this value was higher than those recorded for ceftriaxone in lactating goats (K21=143 h-1

)[9]

in

lactating ewes (K21=125 h-1

)[25]

and in domestic cats (K21=154 h-1

)[15]

The apparent volume of distribution of ceftriaxone was (0355plusmn0004LKg) this value is

nearly similar to that recorded for cefaronide in sheep(039 LKg)[7]

cefotaxime in dog (048

lkg)[39]

in goat (051 lkg)

[40] for caphalexin in buffalo calves (041 Lkg)

[41] for cefipime in

ewes and calves (032 lkg) (043Lkg)[29]

and[30]

respectively For ceftriaxone in domestic

cats (057Lkg)[15]

in camel (032Lkg)[42]

On the other hand this result is differ than that

reported for cefotaxime in buffalo calves (117Lkg)[43]

High value of the volume of

distribution suggested extensive penetration power Drug with volume of distribution greater

than one literkilogram indicated wide distribution or extensive tissue binding or both[44]

The

apparent volume of distribution in the present study indicated moderate tissue penetrating

power This result agreed with[15]

for ceftriaxone in domestic cats

wwwwjppscom Vol 5 Issue 01 2016

1448

Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

Ceftriaxone is eliminated in the current study following a single intravenous injection with

elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the

data recorded for ceftizoxime in goats (624hours)[45]

On contrast this value was longer than

that reported for ceftriaxone in lactating ewe (175hours)[25]

for cefaronide in sheep (17

hours)[7]

For cephalexin in buffulo calves (216hours)[41]

for ceftriaxone in healthy horse

(162hours)[46]

also this value is longer than that recorded for ceftriaxone in lactating goats

(144hours)[9]

for cefipime in goats (186hours)[47]

The rate of total body clearance of ceftriaxone following a single intravenous injection is

0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]

On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating

goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)

(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]

respectively

The variation in total body clearance might be attributed to specific interspecies variation

handling of the drug method used healthy status of the animal[48]

The difference between values calculated for pharmacokinetic parameters may be attributed

to animal species the drug formulation employed the age the size or sex o l lf the animal

or even inter individual variation and also due to method of analysis of the drug[49]

Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the

drug reached its peak serum concentrations after one hour of injection with value

of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12

hours post-injection The reported peak serum concentrations neerly similar to that reported

for cephalexin in buffulo calves (457 microgml)[41]

These results is differed than those reported

for ceftriaxone in cross breed calves (188 microgml at 30 min[16]

in Kangro breed of goats

(Capra Hircus) (2640 microgml at 20 min[10][50]

found after intramuscular administration of

ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher

than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]

The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time

(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats

(4932 microgml[47]

The reported maximum serum concentration (Cmax) is higher than that

reported for ceftriaxone in lactating goats(236 microgml)[9]

in lactating ewes (1722 microgml[25]

in

wwwwjppscom Vol 5 Issue 01 2016

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

goats (2151 microgml)[11]

for cefquinome in camels (123 microgml)[51]

for ceftriaxone in calves

(1534 microgml)[26]

in patanwadi sheep (1553 microgml)[8]

for cefpirome in cattle (101 microgml)[52]

And for ceftiofur in chickens (2594 μgml)[37]

On the other hand the result was lower than

that reported by[6]

who observed the maximum serum concentration (Cmax) of ceftriaxone in

human after ntramuscular administration was (805 microgml) also it was lower than that

reported for ceftriaxone in dog (11510 microgml)[53]

in domestic cats (5440 microgml)[15]

and for

ceftazoxime in goats (8878 microgml)[45]

The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating

ewes by[25]

On contrast it is longer than those reported for ceftriaxone in dogs

(129hours)[53]

for ceftriaxone in lactating goats (07hours)[9]

also the result was longer than

that reported for ceftriaxone in domestic cats (033hours)[15]

in buffulo calves (05 hours)[13]

and for cefpirome in cattle (075hours)[52]

The reported [tmax] is shorter than those reported

for cefquinome in camels (425hours)[51]

in sheep and goats (261 and 262 hours)[36]

and for

ceftiofur in chickens (251 hours)[37]

The elimination half life [t05(β)]

following a single intramuscular administration was 1804 hours This value is nearly agreed

with that recorded for cefquinomein camels (1024hours)[52]

On contrast this result is longer

than that reported for cephalexin in buffalo calves (243hours)[41]

for ceftriaxone in lactating

ewes (177hours)[25]

in buffalo calves (438hours)[13]

in goats (203 hours)[11]

and for

cefipime in goats (165 hours)[47]

The rate of total body clearance of ceftriaxone following a single intramuscular injection is

0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves

(401Lkgh)[13]

in goats (304 Lkgh)[11]

and in sheep (222 Lkgh)[8]

Bioavailability is the fraction of the drug administered by non vascular rout that gains

accesses to the systemic circulation The obtained result revealed that the calculated systemic

bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves

(61)[54]

It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]

On the other

hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]

for ceftriaxone in goats (59)[11]

in calves (47)[55]

On contrast this value is lower than

those reported for cefotaxime in two cats 982 and 93)[57]

for cephradine in goats

wwwwjppscom Vol 5 Issue 01 2016

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

(739)[58]

for ceftazidime in a rabbit (966)[27]

for ceftriaxone in lactating goats (85)[9]

in lactating ewes (836)[25]

in domestic cats 8572[15]

for cefipime in goats 8645[47]

for ceftriaxone in buffulo calves 702[13]

and for ceftiofur in chickens 8890[37]

Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium

infected goats twics dialy for five days revealed that the drug could be detected in a

therapeutic level for 12hours following repeated intramuscular administrations and exceeded

the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]

The relative higher serum concentrations of ceftriaxone after the last dose compared to the

first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12

hours intervals for five consecutive days These observations agreed with data reported by[36]

on comparing the data of serum levels of repeated intramuscular injections with first

intramuscular injection it was revealed that repeated intramuscular injections of cefquinome

have cumulative effect in both species sheep and goats

The obtained result is inconsistent with that reported by[56]

who found thatwhen cefotaxime

was administered repetitively in patients the ratio of maximal serum levels after the last dose

to those after the first dose demonstrated minimal accumulation of intact drug and by[60]

who

found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in

buffalo calves

The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium

infected goats are significantly lower than those in normal goats following repeated

intramuscular injection These lower blood concentrations in Salmonella typhimurium

infected goats might be attributed to the higher penetrating power of ceftriaxone to the

diseased tissues[48]

This phenomenon is similar to data recorded by[61]

who suggested that

Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of

ceftriaxone These alterations might be due to fever and inflammation induced by

infections[59]

proved that the serum concentrations of cephradine following intramuscular

administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after

each intramuscular dose with a lower significant values recorded in Escherichia-coli infected

goats than in normal goatsAlso similer to that reported by[62]

who observed that the

maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep

wwwwjppscom Vol 5 Issue 01 2016

1451

Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

in comparison to normal sheepOn contrast[43]

reported that peak plasma level of cefotaxime

in febrile buffalo calves was higher than healthy buffalo calves

In this study the total body clearance (CLtot) in normal goats are significantly lower than in

Salmonella typhimurium infected goats This result supported by[61]

and[63]

fever and

inflammation are cardinal features in bacterial infection which may in turn caused an

increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all

these could lead to increased in the rate at which the drug was delivered to both organs which

were important sites of drug excretion This might somewhat explain the increase in the total

body clearance in infected goats This result is differ than that reported by[64]

who observed

that the clearance of ceftriaxone was significantly reduced in infected mice than in non

infected animals

The highest concentrations of ceftriaxone in milk are recorded 4 hours after each

intramuscular injection with a significant lower value in Salmonella typhimurium infected

goats than in normal goats This might be attributed to accumulation of drug in the inflammed

tissues[48]

This result is similar to those reported by[6559]

who found that milk concentrations

of gentamicin and cephradine were significantly lower in infected goats and cattle than in

normal ones respectively

The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the

non-ionic passive diffusion principle[66]

reported that most drug cross-lipid membranes by

passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly

influenced by the physicochemical properties of the drug[6768]

Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum

ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the

physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]

Milk

contains substantially more lipid and less protein than serum and is slightly more acidic

Therefore drugs which tend to concentrated in milk are weak bases with low serum protein

binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide

and aminothiazole also possesses an hydroxytriazinone group as new and additional

ionization center[70]

these compounds are sufficiently lipid- soluble to be able to penetrate

tissues

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

The dose of ceftriaxone used in the present study induced therapeutically concentrations in

milk These concentrations suggested that ceftriaxone would be efficacious in treatment of

mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily

for 3-5 days

The study showed that the urine concentrations of ceftriaxone are greater than the concurrent

serum concentrations following intramuscular injection This observation is similar to those

reported in cows after cephapirin administrations[71]

In the present study urine concentrations of ceftriaxone increased with the repetition of

dosing This observation supported by[72]

after repeated intramuscular administrations of

ceftriaxone in healthy volunteeres

The mean peak urine concentrations of ceftriaxone were reached 2 hours after each

intramuscular injection The lower urine ceftriaxone concentrations in Salmonella

typhimurium infected goats than in normal goats might be attributed to the accumulation of

the drug in the inflamed tissues[48]

The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower

ratio in Salmonella typhimurium infected goats than in normal goats at different time of

sampling This indicates that glomerular filteration seemed to be the main pathway of

ceftriaxone elimination This observation supported by[59]

who found that the ratio between

cephradine clearance from blood of goats to creatinine clearance showed a marked decrease

in Escherichia-coli infected goats than in normal goats This indicated that glomerular

filteration seemed to be the main pathway of cephradine elimination with a limited rate of

tubular reabsorption

CONCLUSION

The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value

referred a better absorption of ceftriaxone from its site of intramuscular administration The

high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular

administrations suggested that ceftriaxone could be used for treatment of mastitis caused by

Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats

The high concentrations of ceftriaxone in urine after repeated intramuscular administrations

suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections

wwwwjppscom Vol 5 Issue 01 2016

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in

goats

REFERANCES

1 Neu HC Merpol NJ and Fukp (1981) Antibacterial activity of ceftriaxone

abetalactamase stable cephalosporines Antimicrobial agents and chemotherapy 19

414-423

2 Richard DM Heel RC Brogden RN Speight TM Avery GS (1984) Ceftriaxone a

review of its antibacterial activity pharmacological properties and therapeutic uses

Drugs 27 469-527

3 Brogden RN and Ward A (1988) Ceftriaxone a reappraisal of its antibacterial activity

and pharmacokinetic properties and an update on its therapeutic use with particular

reference to once-daily administration Drugs 35 604-645

4 Waxman DJ and Strominger JL (1983) Penicillin-binding proteins and the

mechanism of action of beta-lactam antibiotics Annu Rev Biochem 52(1) 825-869

5 Christ W (1991) properties of cephalosporines Infestion 19 244-252

6 Goonetilleke AK Dev D Aziz I Hughes C Smith MJ Basran GS (1996) A

comparative analysis of pharmacokinetics of ceftriaxone in serum and pleural fluid in

humans a study of once daily administration by intramuscular intravenous routes J

Antimicrob Chemother Dec 38(6) 969-76

7 Guerrini VH Filippich LJ Cao G R English PB Bourne DW (1985)

Pharmacokinetics of cefaronide ceftriaxone and cefperazone in sheep J Vet Pharmacol

Ther 8(2) 120-7

8 Swati Tiwari S Patel UD Bhavsar SK and Thaker AM (2010) Pharmacokinetics

and Bioavailability of Ceftriaxone in Patanwadi Sheep Online veterinary journal 5(2)

9 Ismail MM (2005) Pharmacokinetics urinary and mammary excretion of ceftriaxone in

lactating goats J Vet Med A Physiol Pathol Clin Med Sep 52(7) 354-8

10 Rajinder R prawez S Srivastiva AS (2005) Pharmacokinetics and dosage regimen of

ceftriaxone following its single ntramuscular adminsteration in kagani breed of goats

(Capra Hircus) Journal of reaserch 4(2) 91-93

11 Tiwari S Swati Bhavsar SK Patel UD and Thaker AM (2009) Disposition of

Ceftriaxone in Goats (Capra hircus) Online veterinary journal 4(2)

12 Dardi MS Sharma SK and Srivastava AK (2004) Pharmacokinetics and Dosage

regimen of ceftriaxone in buffalo calves Vet Res Commun 28 331-338

wwwwjppscom Vol 5 Issue 02 2016

1446

Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences

Table (10) Ceftriaxone clearancecreatinine clearance following repeated ntramuscular injection of 20 mg

ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats

(n=4)

Dose Time of

a administration

(h)

Ninth_

(XplusmnS E)

Seventh_

(XplusmnS E)

Fifth_

(XplusmnS E)

Third_

(XplusmnS E)

First_

(XplusmnS E)fi

S N S N S N N S N S S N

0934plusmn0083 0305plusmn0013 183plusmn0116 0864plusmn0098 0358plusmn0018 0279plusmn0047 0099plusmn0020 0127plusmn0001 ------- ----------- Before

220plusmn0115 0819plusmn0044 131plusmn00414 0458plusmn0029 0876plusmn0063 126plusmn0068 0361plusmn0011 0813plusmn0031 0018plusmn0003 108plusmn0062 050

164plusmn0078 0818plusmn0029 118plusmn0068 0546plusmn0027 0858plusmn0052 0407plusmn0041 0331plusmn0009 0287plusmn0025 0324plusmn0011 0909plusmn0187 1

161plusmn0044 0488plusmn0005 232plusmn128 0329plusmn0027 169plusmn0464 0686plusmn0050 0409plusmn0020 0220plusmn0029 0512plusmn0077 266plusmn177 2

0933plusmn0024 0394plusmn0005 0948plusmn0062 0296plusmn0007 0381plusmn0027 0160plusmn0008 0235plusmn0014 0083plusmn0006 0528plusmn0028 0362plusmn0041 4

0726plusmn0018 0411plusmn0028 0639plusmn0066 0204plusmn0006 0446plusmn0034 0286plusmn0008 0238plusmn0019 0214plusmn0006 020plusmn0013 0382plusmn0028 6

0609plusmn0072 0425plusmn0036 0508plusmn0052 0192plusmn0009 0524plusmn0146 174plusmn0083 0477plusmn0015 0213plusmn00018 0109plusmn0185 0222plusmn0006 8

108plusmn0128 0496plusmn0012 0942plusmn0004 0265plusmn0030 0891plusmn0056 0706plusmn0103 0351plusmn0022 0354plusmn0018 0111plusmn0021 0098plusmn0018 12

Between normal and diseased

Plt 005 Plt001 Plt0001

N= Normal S= Salmonella infected

DISCUSSION

In the present investigation intravenous injection of 20 mg ceftriaxonekgbwt in normal goats the drug showed high serum level

(92plusmn 0408 μgml) at 5 minutes post-injection then its concentration was decreased gradually till reached its minimum level (18

plusmn0816μgml) at 8hours post-injection

wwwwjppscom Vol 5 Issue 01 2016

1447

Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

In the present investigation the intravenous injection of 20 mg ceftriaxonekgbwt In normal

goats showed that the drug disposition best fitted a two-compartments- open model a

compartment of plasma and rapid equilibrating tissues and a deeper slower compartment

The obtained result is consistent with those reported for ceftriaxone in lactating goats[9]

lactating ewe[25]

domestic cat[15]

calves[26]

and patanwadi sheep[8]

Also this phenomenon is

in agreement with those reported for other cephalosporines as ceftazidime in a rabbit[27]

cefepime in dog and neonatal foals[28]

ewes[29]

ceftriaxone in goats[9]

cefipime in calves[30]

ceftiofur in cross-bred friesian cattle[31]

cefipime in calves[32]

ceftiofur in cows[33]

cefpirome

in cross-bred calves[3]

cefazidime in goats[35]

and cefquinome in sheep and goats[36]

cefipime

in chickens[37]

Ceftriaxone was distributed after intravenous injection with a distribution phase (α) equal to

656 per hour with a short distribution half ndash life [t05 (α)] equal to 0104 hour The shorter

distribution half-life of ceftriaxone in goats suggested the rapid distribution of the drug in

body tissue and fluid and that nearly similar to that recorded for ceftriaxone in lactating

goats(012 hour)[9]

for ceftriaxone in lactating ewes (0152 hour)[2]

and for ceftriaxone in

calves( 013hour)[26]

The rapid distribution of ceftriaxone in goats is supported by high rate constant of transfer of

the drug from central to peripheral compartment [K12 = 353 h-1

] as compared to the rate

constant of transfer of the drug from peripheral to central compartment [K21= 295 h-1

] This

value is nearly similar to those reported for cefotaxime in goats (K21=327 h-1

)[38]

On contrast

this value was higher than those recorded for ceftriaxone in lactating goats (K21=143 h-1

)[9]

in

lactating ewes (K21=125 h-1

)[25]

and in domestic cats (K21=154 h-1

)[15]

The apparent volume of distribution of ceftriaxone was (0355plusmn0004LKg) this value is

nearly similar to that recorded for cefaronide in sheep(039 LKg)[7]

cefotaxime in dog (048

lkg)[39]

in goat (051 lkg)

[40] for caphalexin in buffalo calves (041 Lkg)

[41] for cefipime in

ewes and calves (032 lkg) (043Lkg)[29]

and[30]

respectively For ceftriaxone in domestic

cats (057Lkg)[15]

in camel (032Lkg)[42]

On the other hand this result is differ than that

reported for cefotaxime in buffalo calves (117Lkg)[43]

High value of the volume of

distribution suggested extensive penetration power Drug with volume of distribution greater

than one literkilogram indicated wide distribution or extensive tissue binding or both[44]

The

apparent volume of distribution in the present study indicated moderate tissue penetrating

power This result agreed with[15]

for ceftriaxone in domestic cats

wwwwjppscom Vol 5 Issue 01 2016

1448

Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

Ceftriaxone is eliminated in the current study following a single intravenous injection with

elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the

data recorded for ceftizoxime in goats (624hours)[45]

On contrast this value was longer than

that reported for ceftriaxone in lactating ewe (175hours)[25]

for cefaronide in sheep (17

hours)[7]

For cephalexin in buffulo calves (216hours)[41]

for ceftriaxone in healthy horse

(162hours)[46]

also this value is longer than that recorded for ceftriaxone in lactating goats

(144hours)[9]

for cefipime in goats (186hours)[47]

The rate of total body clearance of ceftriaxone following a single intravenous injection is

0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]

On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating

goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)

(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]

respectively

The variation in total body clearance might be attributed to specific interspecies variation

handling of the drug method used healthy status of the animal[48]

The difference between values calculated for pharmacokinetic parameters may be attributed

to animal species the drug formulation employed the age the size or sex o l lf the animal

or even inter individual variation and also due to method of analysis of the drug[49]

Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the

drug reached its peak serum concentrations after one hour of injection with value

of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12

hours post-injection The reported peak serum concentrations neerly similar to that reported

for cephalexin in buffulo calves (457 microgml)[41]

These results is differed than those reported

for ceftriaxone in cross breed calves (188 microgml at 30 min[16]

in Kangro breed of goats

(Capra Hircus) (2640 microgml at 20 min[10][50]

found after intramuscular administration of

ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher

than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]

The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time

(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats

(4932 microgml[47]

The reported maximum serum concentration (Cmax) is higher than that

reported for ceftriaxone in lactating goats(236 microgml)[9]

in lactating ewes (1722 microgml[25]

in

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

goats (2151 microgml)[11]

for cefquinome in camels (123 microgml)[51]

for ceftriaxone in calves

(1534 microgml)[26]

in patanwadi sheep (1553 microgml)[8]

for cefpirome in cattle (101 microgml)[52]

And for ceftiofur in chickens (2594 μgml)[37]

On the other hand the result was lower than

that reported by[6]

who observed the maximum serum concentration (Cmax) of ceftriaxone in

human after ntramuscular administration was (805 microgml) also it was lower than that

reported for ceftriaxone in dog (11510 microgml)[53]

in domestic cats (5440 microgml)[15]

and for

ceftazoxime in goats (8878 microgml)[45]

The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating

ewes by[25]

On contrast it is longer than those reported for ceftriaxone in dogs

(129hours)[53]

for ceftriaxone in lactating goats (07hours)[9]

also the result was longer than

that reported for ceftriaxone in domestic cats (033hours)[15]

in buffulo calves (05 hours)[13]

and for cefpirome in cattle (075hours)[52]

The reported [tmax] is shorter than those reported

for cefquinome in camels (425hours)[51]

in sheep and goats (261 and 262 hours)[36]

and for

ceftiofur in chickens (251 hours)[37]

The elimination half life [t05(β)]

following a single intramuscular administration was 1804 hours This value is nearly agreed

with that recorded for cefquinomein camels (1024hours)[52]

On contrast this result is longer

than that reported for cephalexin in buffalo calves (243hours)[41]

for ceftriaxone in lactating

ewes (177hours)[25]

in buffalo calves (438hours)[13]

in goats (203 hours)[11]

and for

cefipime in goats (165 hours)[47]

The rate of total body clearance of ceftriaxone following a single intramuscular injection is

0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves

(401Lkgh)[13]

in goats (304 Lkgh)[11]

and in sheep (222 Lkgh)[8]

Bioavailability is the fraction of the drug administered by non vascular rout that gains

accesses to the systemic circulation The obtained result revealed that the calculated systemic

bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves

(61)[54]

It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]

On the other

hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]

for ceftriaxone in goats (59)[11]

in calves (47)[55]

On contrast this value is lower than

those reported for cefotaxime in two cats 982 and 93)[57]

for cephradine in goats

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

(739)[58]

for ceftazidime in a rabbit (966)[27]

for ceftriaxone in lactating goats (85)[9]

in lactating ewes (836)[25]

in domestic cats 8572[15]

for cefipime in goats 8645[47]

for ceftriaxone in buffulo calves 702[13]

and for ceftiofur in chickens 8890[37]

Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium

infected goats twics dialy for five days revealed that the drug could be detected in a

therapeutic level for 12hours following repeated intramuscular administrations and exceeded

the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]

The relative higher serum concentrations of ceftriaxone after the last dose compared to the

first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12

hours intervals for five consecutive days These observations agreed with data reported by[36]

on comparing the data of serum levels of repeated intramuscular injections with first

intramuscular injection it was revealed that repeated intramuscular injections of cefquinome

have cumulative effect in both species sheep and goats

The obtained result is inconsistent with that reported by[56]

who found thatwhen cefotaxime

was administered repetitively in patients the ratio of maximal serum levels after the last dose

to those after the first dose demonstrated minimal accumulation of intact drug and by[60]

who

found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in

buffalo calves

The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium

infected goats are significantly lower than those in normal goats following repeated

intramuscular injection These lower blood concentrations in Salmonella typhimurium

infected goats might be attributed to the higher penetrating power of ceftriaxone to the

diseased tissues[48]

This phenomenon is similar to data recorded by[61]

who suggested that

Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of

ceftriaxone These alterations might be due to fever and inflammation induced by

infections[59]

proved that the serum concentrations of cephradine following intramuscular

administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after

each intramuscular dose with a lower significant values recorded in Escherichia-coli infected

goats than in normal goatsAlso similer to that reported by[62]

who observed that the

maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

in comparison to normal sheepOn contrast[43]

reported that peak plasma level of cefotaxime

in febrile buffalo calves was higher than healthy buffalo calves

In this study the total body clearance (CLtot) in normal goats are significantly lower than in

Salmonella typhimurium infected goats This result supported by[61]

and[63]

fever and

inflammation are cardinal features in bacterial infection which may in turn caused an

increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all

these could lead to increased in the rate at which the drug was delivered to both organs which

were important sites of drug excretion This might somewhat explain the increase in the total

body clearance in infected goats This result is differ than that reported by[64]

who observed

that the clearance of ceftriaxone was significantly reduced in infected mice than in non

infected animals

The highest concentrations of ceftriaxone in milk are recorded 4 hours after each

intramuscular injection with a significant lower value in Salmonella typhimurium infected

goats than in normal goats This might be attributed to accumulation of drug in the inflammed

tissues[48]

This result is similar to those reported by[6559]

who found that milk concentrations

of gentamicin and cephradine were significantly lower in infected goats and cattle than in

normal ones respectively

The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the

non-ionic passive diffusion principle[66]

reported that most drug cross-lipid membranes by

passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly

influenced by the physicochemical properties of the drug[6768]

Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum

ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the

physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]

Milk

contains substantially more lipid and less protein than serum and is slightly more acidic

Therefore drugs which tend to concentrated in milk are weak bases with low serum protein

binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide

and aminothiazole also possesses an hydroxytriazinone group as new and additional

ionization center[70]

these compounds are sufficiently lipid- soluble to be able to penetrate

tissues

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

The dose of ceftriaxone used in the present study induced therapeutically concentrations in

milk These concentrations suggested that ceftriaxone would be efficacious in treatment of

mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily

for 3-5 days

The study showed that the urine concentrations of ceftriaxone are greater than the concurrent

serum concentrations following intramuscular injection This observation is similar to those

reported in cows after cephapirin administrations[71]

In the present study urine concentrations of ceftriaxone increased with the repetition of

dosing This observation supported by[72]

after repeated intramuscular administrations of

ceftriaxone in healthy volunteeres

The mean peak urine concentrations of ceftriaxone were reached 2 hours after each

intramuscular injection The lower urine ceftriaxone concentrations in Salmonella

typhimurium infected goats than in normal goats might be attributed to the accumulation of

the drug in the inflamed tissues[48]

The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower

ratio in Salmonella typhimurium infected goats than in normal goats at different time of

sampling This indicates that glomerular filteration seemed to be the main pathway of

ceftriaxone elimination This observation supported by[59]

who found that the ratio between

cephradine clearance from blood of goats to creatinine clearance showed a marked decrease

in Escherichia-coli infected goats than in normal goats This indicated that glomerular

filteration seemed to be the main pathway of cephradine elimination with a limited rate of

tubular reabsorption

CONCLUSION

The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value

referred a better absorption of ceftriaxone from its site of intramuscular administration The

high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular

administrations suggested that ceftriaxone could be used for treatment of mastitis caused by

Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats

The high concentrations of ceftriaxone in urine after repeated intramuscular administrations

suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in

goats

REFERANCES

1 Neu HC Merpol NJ and Fukp (1981) Antibacterial activity of ceftriaxone

abetalactamase stable cephalosporines Antimicrobial agents and chemotherapy 19

414-423

2 Richard DM Heel RC Brogden RN Speight TM Avery GS (1984) Ceftriaxone a

review of its antibacterial activity pharmacological properties and therapeutic uses

Drugs 27 469-527

3 Brogden RN and Ward A (1988) Ceftriaxone a reappraisal of its antibacterial activity

and pharmacokinetic properties and an update on its therapeutic use with particular

reference to once-daily administration Drugs 35 604-645

4 Waxman DJ and Strominger JL (1983) Penicillin-binding proteins and the

mechanism of action of beta-lactam antibiotics Annu Rev Biochem 52(1) 825-869

5 Christ W (1991) properties of cephalosporines Infestion 19 244-252

6 Goonetilleke AK Dev D Aziz I Hughes C Smith MJ Basran GS (1996) A

comparative analysis of pharmacokinetics of ceftriaxone in serum and pleural fluid in

humans a study of once daily administration by intramuscular intravenous routes J

Antimicrob Chemother Dec 38(6) 969-76

7 Guerrini VH Filippich LJ Cao G R English PB Bourne DW (1985)

Pharmacokinetics of cefaronide ceftriaxone and cefperazone in sheep J Vet Pharmacol

Ther 8(2) 120-7

8 Swati Tiwari S Patel UD Bhavsar SK and Thaker AM (2010) Pharmacokinetics

and Bioavailability of Ceftriaxone in Patanwadi Sheep Online veterinary journal 5(2)

9 Ismail MM (2005) Pharmacokinetics urinary and mammary excretion of ceftriaxone in

lactating goats J Vet Med A Physiol Pathol Clin Med Sep 52(7) 354-8

10 Rajinder R prawez S Srivastiva AS (2005) Pharmacokinetics and dosage regimen of

ceftriaxone following its single ntramuscular adminsteration in kagani breed of goats

(Capra Hircus) Journal of reaserch 4(2) 91-93

11 Tiwari S Swati Bhavsar SK Patel UD and Thaker AM (2009) Disposition of

Ceftriaxone in Goats (Capra hircus) Online veterinary journal 4(2)

12 Dardi MS Sharma SK and Srivastava AK (2004) Pharmacokinetics and Dosage

regimen of ceftriaxone in buffalo calves Vet Res Commun 28 331-338

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

In the present investigation the intravenous injection of 20 mg ceftriaxonekgbwt In normal

goats showed that the drug disposition best fitted a two-compartments- open model a

compartment of plasma and rapid equilibrating tissues and a deeper slower compartment

The obtained result is consistent with those reported for ceftriaxone in lactating goats[9]

lactating ewe[25]

domestic cat[15]

calves[26]

and patanwadi sheep[8]

Also this phenomenon is

in agreement with those reported for other cephalosporines as ceftazidime in a rabbit[27]

cefepime in dog and neonatal foals[28]

ewes[29]

ceftriaxone in goats[9]

cefipime in calves[30]

ceftiofur in cross-bred friesian cattle[31]

cefipime in calves[32]

ceftiofur in cows[33]

cefpirome

in cross-bred calves[3]

cefazidime in goats[35]

and cefquinome in sheep and goats[36]

cefipime

in chickens[37]

Ceftriaxone was distributed after intravenous injection with a distribution phase (α) equal to

656 per hour with a short distribution half ndash life [t05 (α)] equal to 0104 hour The shorter

distribution half-life of ceftriaxone in goats suggested the rapid distribution of the drug in

body tissue and fluid and that nearly similar to that recorded for ceftriaxone in lactating

goats(012 hour)[9]

for ceftriaxone in lactating ewes (0152 hour)[2]

and for ceftriaxone in

calves( 013hour)[26]

The rapid distribution of ceftriaxone in goats is supported by high rate constant of transfer of

the drug from central to peripheral compartment [K12 = 353 h-1

] as compared to the rate

constant of transfer of the drug from peripheral to central compartment [K21= 295 h-1

] This

value is nearly similar to those reported for cefotaxime in goats (K21=327 h-1

)[38]

On contrast

this value was higher than those recorded for ceftriaxone in lactating goats (K21=143 h-1

)[9]

in

lactating ewes (K21=125 h-1

)[25]

and in domestic cats (K21=154 h-1

)[15]

The apparent volume of distribution of ceftriaxone was (0355plusmn0004LKg) this value is

nearly similar to that recorded for cefaronide in sheep(039 LKg)[7]

cefotaxime in dog (048

lkg)[39]

in goat (051 lkg)

[40] for caphalexin in buffalo calves (041 Lkg)

[41] for cefipime in

ewes and calves (032 lkg) (043Lkg)[29]

and[30]

respectively For ceftriaxone in domestic

cats (057Lkg)[15]

in camel (032Lkg)[42]

On the other hand this result is differ than that

reported for cefotaxime in buffalo calves (117Lkg)[43]

High value of the volume of

distribution suggested extensive penetration power Drug with volume of distribution greater

than one literkilogram indicated wide distribution or extensive tissue binding or both[44]

The

apparent volume of distribution in the present study indicated moderate tissue penetrating

power This result agreed with[15]

for ceftriaxone in domestic cats

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

Ceftriaxone is eliminated in the current study following a single intravenous injection with

elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the

data recorded for ceftizoxime in goats (624hours)[45]

On contrast this value was longer than

that reported for ceftriaxone in lactating ewe (175hours)[25]

for cefaronide in sheep (17

hours)[7]

For cephalexin in buffulo calves (216hours)[41]

for ceftriaxone in healthy horse

(162hours)[46]

also this value is longer than that recorded for ceftriaxone in lactating goats

(144hours)[9]

for cefipime in goats (186hours)[47]

The rate of total body clearance of ceftriaxone following a single intravenous injection is

0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]

On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating

goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)

(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]

respectively

The variation in total body clearance might be attributed to specific interspecies variation

handling of the drug method used healthy status of the animal[48]

The difference between values calculated for pharmacokinetic parameters may be attributed

to animal species the drug formulation employed the age the size or sex o l lf the animal

or even inter individual variation and also due to method of analysis of the drug[49]

Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the

drug reached its peak serum concentrations after one hour of injection with value

of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12

hours post-injection The reported peak serum concentrations neerly similar to that reported

for cephalexin in buffulo calves (457 microgml)[41]

These results is differed than those reported

for ceftriaxone in cross breed calves (188 microgml at 30 min[16]

in Kangro breed of goats

(Capra Hircus) (2640 microgml at 20 min[10][50]

found after intramuscular administration of

ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher

than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]

The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time

(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats

(4932 microgml[47]

The reported maximum serum concentration (Cmax) is higher than that

reported for ceftriaxone in lactating goats(236 microgml)[9]

in lactating ewes (1722 microgml[25]

in

wwwwjppscom Vol 5 Issue 01 2016

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

goats (2151 microgml)[11]

for cefquinome in camels (123 microgml)[51]

for ceftriaxone in calves

(1534 microgml)[26]

in patanwadi sheep (1553 microgml)[8]

for cefpirome in cattle (101 microgml)[52]

And for ceftiofur in chickens (2594 μgml)[37]

On the other hand the result was lower than

that reported by[6]

who observed the maximum serum concentration (Cmax) of ceftriaxone in

human after ntramuscular administration was (805 microgml) also it was lower than that

reported for ceftriaxone in dog (11510 microgml)[53]

in domestic cats (5440 microgml)[15]

and for

ceftazoxime in goats (8878 microgml)[45]

The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating

ewes by[25]

On contrast it is longer than those reported for ceftriaxone in dogs

(129hours)[53]

for ceftriaxone in lactating goats (07hours)[9]

also the result was longer than

that reported for ceftriaxone in domestic cats (033hours)[15]

in buffulo calves (05 hours)[13]

and for cefpirome in cattle (075hours)[52]

The reported [tmax] is shorter than those reported

for cefquinome in camels (425hours)[51]

in sheep and goats (261 and 262 hours)[36]

and for

ceftiofur in chickens (251 hours)[37]

The elimination half life [t05(β)]

following a single intramuscular administration was 1804 hours This value is nearly agreed

with that recorded for cefquinomein camels (1024hours)[52]

On contrast this result is longer

than that reported for cephalexin in buffalo calves (243hours)[41]

for ceftriaxone in lactating

ewes (177hours)[25]

in buffalo calves (438hours)[13]

in goats (203 hours)[11]

and for

cefipime in goats (165 hours)[47]

The rate of total body clearance of ceftriaxone following a single intramuscular injection is

0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves

(401Lkgh)[13]

in goats (304 Lkgh)[11]

and in sheep (222 Lkgh)[8]

Bioavailability is the fraction of the drug administered by non vascular rout that gains

accesses to the systemic circulation The obtained result revealed that the calculated systemic

bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves

(61)[54]

It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]

On the other

hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]

for ceftriaxone in goats (59)[11]

in calves (47)[55]

On contrast this value is lower than

those reported for cefotaxime in two cats 982 and 93)[57]

for cephradine in goats

wwwwjppscom Vol 5 Issue 01 2016

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

(739)[58]

for ceftazidime in a rabbit (966)[27]

for ceftriaxone in lactating goats (85)[9]

in lactating ewes (836)[25]

in domestic cats 8572[15]

for cefipime in goats 8645[47]

for ceftriaxone in buffulo calves 702[13]

and for ceftiofur in chickens 8890[37]

Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium

infected goats twics dialy for five days revealed that the drug could be detected in a

therapeutic level for 12hours following repeated intramuscular administrations and exceeded

the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]

The relative higher serum concentrations of ceftriaxone after the last dose compared to the

first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12

hours intervals for five consecutive days These observations agreed with data reported by[36]

on comparing the data of serum levels of repeated intramuscular injections with first

intramuscular injection it was revealed that repeated intramuscular injections of cefquinome

have cumulative effect in both species sheep and goats

The obtained result is inconsistent with that reported by[56]

who found thatwhen cefotaxime

was administered repetitively in patients the ratio of maximal serum levels after the last dose

to those after the first dose demonstrated minimal accumulation of intact drug and by[60]

who

found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in

buffalo calves

The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium

infected goats are significantly lower than those in normal goats following repeated

intramuscular injection These lower blood concentrations in Salmonella typhimurium

infected goats might be attributed to the higher penetrating power of ceftriaxone to the

diseased tissues[48]

This phenomenon is similar to data recorded by[61]

who suggested that

Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of

ceftriaxone These alterations might be due to fever and inflammation induced by

infections[59]

proved that the serum concentrations of cephradine following intramuscular

administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after

each intramuscular dose with a lower significant values recorded in Escherichia-coli infected

goats than in normal goatsAlso similer to that reported by[62]

who observed that the

maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep

wwwwjppscom Vol 5 Issue 01 2016

1451

Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

in comparison to normal sheepOn contrast[43]

reported that peak plasma level of cefotaxime

in febrile buffalo calves was higher than healthy buffalo calves

In this study the total body clearance (CLtot) in normal goats are significantly lower than in

Salmonella typhimurium infected goats This result supported by[61]

and[63]

fever and

inflammation are cardinal features in bacterial infection which may in turn caused an

increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all

these could lead to increased in the rate at which the drug was delivered to both organs which

were important sites of drug excretion This might somewhat explain the increase in the total

body clearance in infected goats This result is differ than that reported by[64]

who observed

that the clearance of ceftriaxone was significantly reduced in infected mice than in non

infected animals

The highest concentrations of ceftriaxone in milk are recorded 4 hours after each

intramuscular injection with a significant lower value in Salmonella typhimurium infected

goats than in normal goats This might be attributed to accumulation of drug in the inflammed

tissues[48]

This result is similar to those reported by[6559]

who found that milk concentrations

of gentamicin and cephradine were significantly lower in infected goats and cattle than in

normal ones respectively

The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the

non-ionic passive diffusion principle[66]

reported that most drug cross-lipid membranes by

passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly

influenced by the physicochemical properties of the drug[6768]

Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum

ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the

physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]

Milk

contains substantially more lipid and less protein than serum and is slightly more acidic

Therefore drugs which tend to concentrated in milk are weak bases with low serum protein

binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide

and aminothiazole also possesses an hydroxytriazinone group as new and additional

ionization center[70]

these compounds are sufficiently lipid- soluble to be able to penetrate

tissues

wwwwjppscom Vol 5 Issue 01 2016

1452

Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

The dose of ceftriaxone used in the present study induced therapeutically concentrations in

milk These concentrations suggested that ceftriaxone would be efficacious in treatment of

mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily

for 3-5 days

The study showed that the urine concentrations of ceftriaxone are greater than the concurrent

serum concentrations following intramuscular injection This observation is similar to those

reported in cows after cephapirin administrations[71]

In the present study urine concentrations of ceftriaxone increased with the repetition of

dosing This observation supported by[72]

after repeated intramuscular administrations of

ceftriaxone in healthy volunteeres

The mean peak urine concentrations of ceftriaxone were reached 2 hours after each

intramuscular injection The lower urine ceftriaxone concentrations in Salmonella

typhimurium infected goats than in normal goats might be attributed to the accumulation of

the drug in the inflamed tissues[48]

The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower

ratio in Salmonella typhimurium infected goats than in normal goats at different time of

sampling This indicates that glomerular filteration seemed to be the main pathway of

ceftriaxone elimination This observation supported by[59]

who found that the ratio between

cephradine clearance from blood of goats to creatinine clearance showed a marked decrease

in Escherichia-coli infected goats than in normal goats This indicated that glomerular

filteration seemed to be the main pathway of cephradine elimination with a limited rate of

tubular reabsorption

CONCLUSION

The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value

referred a better absorption of ceftriaxone from its site of intramuscular administration The

high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular

administrations suggested that ceftriaxone could be used for treatment of mastitis caused by

Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats

The high concentrations of ceftriaxone in urine after repeated intramuscular administrations

suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections

wwwwjppscom Vol 5 Issue 01 2016

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in

goats

REFERANCES

1 Neu HC Merpol NJ and Fukp (1981) Antibacterial activity of ceftriaxone

abetalactamase stable cephalosporines Antimicrobial agents and chemotherapy 19

414-423

2 Richard DM Heel RC Brogden RN Speight TM Avery GS (1984) Ceftriaxone a

review of its antibacterial activity pharmacological properties and therapeutic uses

Drugs 27 469-527

3 Brogden RN and Ward A (1988) Ceftriaxone a reappraisal of its antibacterial activity

and pharmacokinetic properties and an update on its therapeutic use with particular

reference to once-daily administration Drugs 35 604-645

4 Waxman DJ and Strominger JL (1983) Penicillin-binding proteins and the

mechanism of action of beta-lactam antibiotics Annu Rev Biochem 52(1) 825-869

5 Christ W (1991) properties of cephalosporines Infestion 19 244-252

6 Goonetilleke AK Dev D Aziz I Hughes C Smith MJ Basran GS (1996) A

comparative analysis of pharmacokinetics of ceftriaxone in serum and pleural fluid in

humans a study of once daily administration by intramuscular intravenous routes J

Antimicrob Chemother Dec 38(6) 969-76

7 Guerrini VH Filippich LJ Cao G R English PB Bourne DW (1985)

Pharmacokinetics of cefaronide ceftriaxone and cefperazone in sheep J Vet Pharmacol

Ther 8(2) 120-7

8 Swati Tiwari S Patel UD Bhavsar SK and Thaker AM (2010) Pharmacokinetics

and Bioavailability of Ceftriaxone in Patanwadi Sheep Online veterinary journal 5(2)

9 Ismail MM (2005) Pharmacokinetics urinary and mammary excretion of ceftriaxone in

lactating goats J Vet Med A Physiol Pathol Clin Med Sep 52(7) 354-8

10 Rajinder R prawez S Srivastiva AS (2005) Pharmacokinetics and dosage regimen of

ceftriaxone following its single ntramuscular adminsteration in kagani breed of goats

(Capra Hircus) Journal of reaserch 4(2) 91-93

11 Tiwari S Swati Bhavsar SK Patel UD and Thaker AM (2009) Disposition of

Ceftriaxone in Goats (Capra hircus) Online veterinary journal 4(2)

12 Dardi MS Sharma SK and Srivastava AK (2004) Pharmacokinetics and Dosage

regimen of ceftriaxone in buffalo calves Vet Res Commun 28 331-338

wwwwjppscom Vol 5 Issue 01 2016

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

Ceftriaxone is eliminated in the current study following a single intravenous injection with

elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the

data recorded for ceftizoxime in goats (624hours)[45]

On contrast this value was longer than

that reported for ceftriaxone in lactating ewe (175hours)[25]

for cefaronide in sheep (17

hours)[7]

For cephalexin in buffulo calves (216hours)[41]

for ceftriaxone in healthy horse

(162hours)[46]

also this value is longer than that recorded for ceftriaxone in lactating goats

(144hours)[9]

for cefipime in goats (186hours)[47]

The rate of total body clearance of ceftriaxone following a single intravenous injection is

0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]

On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating

goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)

(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]

respectively

The variation in total body clearance might be attributed to specific interspecies variation

handling of the drug method used healthy status of the animal[48]

The difference between values calculated for pharmacokinetic parameters may be attributed

to animal species the drug formulation employed the age the size or sex o l lf the animal

or even inter individual variation and also due to method of analysis of the drug[49]

Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the

drug reached its peak serum concentrations after one hour of injection with value

of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12

hours post-injection The reported peak serum concentrations neerly similar to that reported

for cephalexin in buffulo calves (457 microgml)[41]

These results is differed than those reported

for ceftriaxone in cross breed calves (188 microgml at 30 min[16]

in Kangro breed of goats

(Capra Hircus) (2640 microgml at 20 min[10][50]

found after intramuscular administration of

ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher

than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]

The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time

(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats

(4932 microgml[47]

The reported maximum serum concentration (Cmax) is higher than that

reported for ceftriaxone in lactating goats(236 microgml)[9]

in lactating ewes (1722 microgml[25]

in

wwwwjppscom Vol 5 Issue 01 2016

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

goats (2151 microgml)[11]

for cefquinome in camels (123 microgml)[51]

for ceftriaxone in calves

(1534 microgml)[26]

in patanwadi sheep (1553 microgml)[8]

for cefpirome in cattle (101 microgml)[52]

And for ceftiofur in chickens (2594 μgml)[37]

On the other hand the result was lower than

that reported by[6]

who observed the maximum serum concentration (Cmax) of ceftriaxone in

human after ntramuscular administration was (805 microgml) also it was lower than that

reported for ceftriaxone in dog (11510 microgml)[53]

in domestic cats (5440 microgml)[15]

and for

ceftazoxime in goats (8878 microgml)[45]

The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating

ewes by[25]

On contrast it is longer than those reported for ceftriaxone in dogs

(129hours)[53]

for ceftriaxone in lactating goats (07hours)[9]

also the result was longer than

that reported for ceftriaxone in domestic cats (033hours)[15]

in buffulo calves (05 hours)[13]

and for cefpirome in cattle (075hours)[52]

The reported [tmax] is shorter than those reported

for cefquinome in camels (425hours)[51]

in sheep and goats (261 and 262 hours)[36]

and for

ceftiofur in chickens (251 hours)[37]

The elimination half life [t05(β)]

following a single intramuscular administration was 1804 hours This value is nearly agreed

with that recorded for cefquinomein camels (1024hours)[52]

On contrast this result is longer

than that reported for cephalexin in buffalo calves (243hours)[41]

for ceftriaxone in lactating

ewes (177hours)[25]

in buffalo calves (438hours)[13]

in goats (203 hours)[11]

and for

cefipime in goats (165 hours)[47]

The rate of total body clearance of ceftriaxone following a single intramuscular injection is

0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves

(401Lkgh)[13]

in goats (304 Lkgh)[11]

and in sheep (222 Lkgh)[8]

Bioavailability is the fraction of the drug administered by non vascular rout that gains

accesses to the systemic circulation The obtained result revealed that the calculated systemic

bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves

(61)[54]

It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]

On the other

hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]

for ceftriaxone in goats (59)[11]

in calves (47)[55]

On contrast this value is lower than

those reported for cefotaxime in two cats 982 and 93)[57]

for cephradine in goats

wwwwjppscom Vol 5 Issue 01 2016

1450

Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

(739)[58]

for ceftazidime in a rabbit (966)[27]

for ceftriaxone in lactating goats (85)[9]

in lactating ewes (836)[25]

in domestic cats 8572[15]

for cefipime in goats 8645[47]

for ceftriaxone in buffulo calves 702[13]

and for ceftiofur in chickens 8890[37]

Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium

infected goats twics dialy for five days revealed that the drug could be detected in a

therapeutic level for 12hours following repeated intramuscular administrations and exceeded

the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]

The relative higher serum concentrations of ceftriaxone after the last dose compared to the

first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12

hours intervals for five consecutive days These observations agreed with data reported by[36]

on comparing the data of serum levels of repeated intramuscular injections with first

intramuscular injection it was revealed that repeated intramuscular injections of cefquinome

have cumulative effect in both species sheep and goats

The obtained result is inconsistent with that reported by[56]

who found thatwhen cefotaxime

was administered repetitively in patients the ratio of maximal serum levels after the last dose

to those after the first dose demonstrated minimal accumulation of intact drug and by[60]

who

found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in

buffalo calves

The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium

infected goats are significantly lower than those in normal goats following repeated

intramuscular injection These lower blood concentrations in Salmonella typhimurium

infected goats might be attributed to the higher penetrating power of ceftriaxone to the

diseased tissues[48]

This phenomenon is similar to data recorded by[61]

who suggested that

Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of

ceftriaxone These alterations might be due to fever and inflammation induced by

infections[59]

proved that the serum concentrations of cephradine following intramuscular

administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after

each intramuscular dose with a lower significant values recorded in Escherichia-coli infected

goats than in normal goatsAlso similer to that reported by[62]

who observed that the

maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep

wwwwjppscom Vol 5 Issue 01 2016

1451

Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

in comparison to normal sheepOn contrast[43]

reported that peak plasma level of cefotaxime

in febrile buffalo calves was higher than healthy buffalo calves

In this study the total body clearance (CLtot) in normal goats are significantly lower than in

Salmonella typhimurium infected goats This result supported by[61]

and[63]

fever and

inflammation are cardinal features in bacterial infection which may in turn caused an

increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all

these could lead to increased in the rate at which the drug was delivered to both organs which

were important sites of drug excretion This might somewhat explain the increase in the total

body clearance in infected goats This result is differ than that reported by[64]

who observed

that the clearance of ceftriaxone was significantly reduced in infected mice than in non

infected animals

The highest concentrations of ceftriaxone in milk are recorded 4 hours after each

intramuscular injection with a significant lower value in Salmonella typhimurium infected

goats than in normal goats This might be attributed to accumulation of drug in the inflammed

tissues[48]

This result is similar to those reported by[6559]

who found that milk concentrations

of gentamicin and cephradine were significantly lower in infected goats and cattle than in

normal ones respectively

The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the

non-ionic passive diffusion principle[66]

reported that most drug cross-lipid membranes by

passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly

influenced by the physicochemical properties of the drug[6768]

Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum

ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the

physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]

Milk

contains substantially more lipid and less protein than serum and is slightly more acidic

Therefore drugs which tend to concentrated in milk are weak bases with low serum protein

binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide

and aminothiazole also possesses an hydroxytriazinone group as new and additional

ionization center[70]

these compounds are sufficiently lipid- soluble to be able to penetrate

tissues

wwwwjppscom Vol 5 Issue 01 2016

1452

Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

The dose of ceftriaxone used in the present study induced therapeutically concentrations in

milk These concentrations suggested that ceftriaxone would be efficacious in treatment of

mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily

for 3-5 days

The study showed that the urine concentrations of ceftriaxone are greater than the concurrent

serum concentrations following intramuscular injection This observation is similar to those

reported in cows after cephapirin administrations[71]

In the present study urine concentrations of ceftriaxone increased with the repetition of

dosing This observation supported by[72]

after repeated intramuscular administrations of

ceftriaxone in healthy volunteeres

The mean peak urine concentrations of ceftriaxone were reached 2 hours after each

intramuscular injection The lower urine ceftriaxone concentrations in Salmonella

typhimurium infected goats than in normal goats might be attributed to the accumulation of

the drug in the inflamed tissues[48]

The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower

ratio in Salmonella typhimurium infected goats than in normal goats at different time of

sampling This indicates that glomerular filteration seemed to be the main pathway of

ceftriaxone elimination This observation supported by[59]

who found that the ratio between

cephradine clearance from blood of goats to creatinine clearance showed a marked decrease

in Escherichia-coli infected goats than in normal goats This indicated that glomerular

filteration seemed to be the main pathway of cephradine elimination with a limited rate of

tubular reabsorption

CONCLUSION

The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value

referred a better absorption of ceftriaxone from its site of intramuscular administration The

high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular

administrations suggested that ceftriaxone could be used for treatment of mastitis caused by

Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats

The high concentrations of ceftriaxone in urine after repeated intramuscular administrations

suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections

wwwwjppscom Vol 5 Issue 01 2016

1453

Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in

goats

REFERANCES

1 Neu HC Merpol NJ and Fukp (1981) Antibacterial activity of ceftriaxone

abetalactamase stable cephalosporines Antimicrobial agents and chemotherapy 19

414-423

2 Richard DM Heel RC Brogden RN Speight TM Avery GS (1984) Ceftriaxone a

review of its antibacterial activity pharmacological properties and therapeutic uses

Drugs 27 469-527

3 Brogden RN and Ward A (1988) Ceftriaxone a reappraisal of its antibacterial activity

and pharmacokinetic properties and an update on its therapeutic use with particular

reference to once-daily administration Drugs 35 604-645

4 Waxman DJ and Strominger JL (1983) Penicillin-binding proteins and the

mechanism of action of beta-lactam antibiotics Annu Rev Biochem 52(1) 825-869

5 Christ W (1991) properties of cephalosporines Infestion 19 244-252

6 Goonetilleke AK Dev D Aziz I Hughes C Smith MJ Basran GS (1996) A

comparative analysis of pharmacokinetics of ceftriaxone in serum and pleural fluid in

humans a study of once daily administration by intramuscular intravenous routes J

Antimicrob Chemother Dec 38(6) 969-76

7 Guerrini VH Filippich LJ Cao G R English PB Bourne DW (1985)

Pharmacokinetics of cefaronide ceftriaxone and cefperazone in sheep J Vet Pharmacol

Ther 8(2) 120-7

8 Swati Tiwari S Patel UD Bhavsar SK and Thaker AM (2010) Pharmacokinetics

and Bioavailability of Ceftriaxone in Patanwadi Sheep Online veterinary journal 5(2)

9 Ismail MM (2005) Pharmacokinetics urinary and mammary excretion of ceftriaxone in

lactating goats J Vet Med A Physiol Pathol Clin Med Sep 52(7) 354-8

10 Rajinder R prawez S Srivastiva AS (2005) Pharmacokinetics and dosage regimen of

ceftriaxone following its single ntramuscular adminsteration in kagani breed of goats

(Capra Hircus) Journal of reaserch 4(2) 91-93

11 Tiwari S Swati Bhavsar SK Patel UD and Thaker AM (2009) Disposition of

Ceftriaxone in Goats (Capra hircus) Online veterinary journal 4(2)

12 Dardi MS Sharma SK and Srivastava AK (2004) Pharmacokinetics and Dosage

regimen of ceftriaxone in buffalo calves Vet Res Commun 28 331-338

wwwwjppscom Vol 5 Issue 01 2016

1449

Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

goats (2151 microgml)[11]

for cefquinome in camels (123 microgml)[51]

for ceftriaxone in calves

(1534 microgml)[26]

in patanwadi sheep (1553 microgml)[8]

for cefpirome in cattle (101 microgml)[52]

And for ceftiofur in chickens (2594 μgml)[37]

On the other hand the result was lower than

that reported by[6]

who observed the maximum serum concentration (Cmax) of ceftriaxone in

human after ntramuscular administration was (805 microgml) also it was lower than that

reported for ceftriaxone in dog (11510 microgml)[53]

in domestic cats (5440 microgml)[15]

and for

ceftazoxime in goats (8878 microgml)[45]

The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating

ewes by[25]

On contrast it is longer than those reported for ceftriaxone in dogs

(129hours)[53]

for ceftriaxone in lactating goats (07hours)[9]

also the result was longer than

that reported for ceftriaxone in domestic cats (033hours)[15]

in buffulo calves (05 hours)[13]

and for cefpirome in cattle (075hours)[52]

The reported [tmax] is shorter than those reported

for cefquinome in camels (425hours)[51]

in sheep and goats (261 and 262 hours)[36]

and for

ceftiofur in chickens (251 hours)[37]

The elimination half life [t05(β)]

following a single intramuscular administration was 1804 hours This value is nearly agreed

with that recorded for cefquinomein camels (1024hours)[52]

On contrast this result is longer

than that reported for cephalexin in buffalo calves (243hours)[41]

for ceftriaxone in lactating

ewes (177hours)[25]

in buffalo calves (438hours)[13]

in goats (203 hours)[11]

and for

cefipime in goats (165 hours)[47]

The rate of total body clearance of ceftriaxone following a single intramuscular injection is

0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves

(401Lkgh)[13]

in goats (304 Lkgh)[11]

and in sheep (222 Lkgh)[8]

Bioavailability is the fraction of the drug administered by non vascular rout that gains

accesses to the systemic circulation The obtained result revealed that the calculated systemic

bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves

(61)[54]

It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]

On the other

hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]

for ceftriaxone in goats (59)[11]

in calves (47)[55]

On contrast this value is lower than

those reported for cefotaxime in two cats 982 and 93)[57]

for cephradine in goats

wwwwjppscom Vol 5 Issue 01 2016

1450

Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

(739)[58]

for ceftazidime in a rabbit (966)[27]

for ceftriaxone in lactating goats (85)[9]

in lactating ewes (836)[25]

in domestic cats 8572[15]

for cefipime in goats 8645[47]

for ceftriaxone in buffulo calves 702[13]

and for ceftiofur in chickens 8890[37]

Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium

infected goats twics dialy for five days revealed that the drug could be detected in a

therapeutic level for 12hours following repeated intramuscular administrations and exceeded

the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]

The relative higher serum concentrations of ceftriaxone after the last dose compared to the

first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12

hours intervals for five consecutive days These observations agreed with data reported by[36]

on comparing the data of serum levels of repeated intramuscular injections with first

intramuscular injection it was revealed that repeated intramuscular injections of cefquinome

have cumulative effect in both species sheep and goats

The obtained result is inconsistent with that reported by[56]

who found thatwhen cefotaxime

was administered repetitively in patients the ratio of maximal serum levels after the last dose

to those after the first dose demonstrated minimal accumulation of intact drug and by[60]

who

found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in

buffalo calves

The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium

infected goats are significantly lower than those in normal goats following repeated

intramuscular injection These lower blood concentrations in Salmonella typhimurium

infected goats might be attributed to the higher penetrating power of ceftriaxone to the

diseased tissues[48]

This phenomenon is similar to data recorded by[61]

who suggested that

Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of

ceftriaxone These alterations might be due to fever and inflammation induced by

infections[59]

proved that the serum concentrations of cephradine following intramuscular

administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after

each intramuscular dose with a lower significant values recorded in Escherichia-coli infected

goats than in normal goatsAlso similer to that reported by[62]

who observed that the

maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep

wwwwjppscom Vol 5 Issue 01 2016

1451

Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

in comparison to normal sheepOn contrast[43]

reported that peak plasma level of cefotaxime

in febrile buffalo calves was higher than healthy buffalo calves

In this study the total body clearance (CLtot) in normal goats are significantly lower than in

Salmonella typhimurium infected goats This result supported by[61]

and[63]

fever and

inflammation are cardinal features in bacterial infection which may in turn caused an

increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all

these could lead to increased in the rate at which the drug was delivered to both organs which

were important sites of drug excretion This might somewhat explain the increase in the total

body clearance in infected goats This result is differ than that reported by[64]

who observed

that the clearance of ceftriaxone was significantly reduced in infected mice than in non

infected animals

The highest concentrations of ceftriaxone in milk are recorded 4 hours after each

intramuscular injection with a significant lower value in Salmonella typhimurium infected

goats than in normal goats This might be attributed to accumulation of drug in the inflammed

tissues[48]

This result is similar to those reported by[6559]

who found that milk concentrations

of gentamicin and cephradine were significantly lower in infected goats and cattle than in

normal ones respectively

The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the

non-ionic passive diffusion principle[66]

reported that most drug cross-lipid membranes by

passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly

influenced by the physicochemical properties of the drug[6768]

Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum

ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the

physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]

Milk

contains substantially more lipid and less protein than serum and is slightly more acidic

Therefore drugs which tend to concentrated in milk are weak bases with low serum protein

binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide

and aminothiazole also possesses an hydroxytriazinone group as new and additional

ionization center[70]

these compounds are sufficiently lipid- soluble to be able to penetrate

tissues

wwwwjppscom Vol 5 Issue 01 2016

1452

Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

The dose of ceftriaxone used in the present study induced therapeutically concentrations in

milk These concentrations suggested that ceftriaxone would be efficacious in treatment of

mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily

for 3-5 days

The study showed that the urine concentrations of ceftriaxone are greater than the concurrent

serum concentrations following intramuscular injection This observation is similar to those

reported in cows after cephapirin administrations[71]

In the present study urine concentrations of ceftriaxone increased with the repetition of

dosing This observation supported by[72]

after repeated intramuscular administrations of

ceftriaxone in healthy volunteeres

The mean peak urine concentrations of ceftriaxone were reached 2 hours after each

intramuscular injection The lower urine ceftriaxone concentrations in Salmonella

typhimurium infected goats than in normal goats might be attributed to the accumulation of

the drug in the inflamed tissues[48]

The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower

ratio in Salmonella typhimurium infected goats than in normal goats at different time of

sampling This indicates that glomerular filteration seemed to be the main pathway of

ceftriaxone elimination This observation supported by[59]

who found that the ratio between

cephradine clearance from blood of goats to creatinine clearance showed a marked decrease

in Escherichia-coli infected goats than in normal goats This indicated that glomerular

filteration seemed to be the main pathway of cephradine elimination with a limited rate of

tubular reabsorption

CONCLUSION

The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value

referred a better absorption of ceftriaxone from its site of intramuscular administration The

high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular

administrations suggested that ceftriaxone could be used for treatment of mastitis caused by

Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats

The high concentrations of ceftriaxone in urine after repeated intramuscular administrations

suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections

wwwwjppscom Vol 5 Issue 01 2016

1453

Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in

goats

REFERANCES

1 Neu HC Merpol NJ and Fukp (1981) Antibacterial activity of ceftriaxone

abetalactamase stable cephalosporines Antimicrobial agents and chemotherapy 19

414-423

2 Richard DM Heel RC Brogden RN Speight TM Avery GS (1984) Ceftriaxone a

review of its antibacterial activity pharmacological properties and therapeutic uses

Drugs 27 469-527

3 Brogden RN and Ward A (1988) Ceftriaxone a reappraisal of its antibacterial activity

and pharmacokinetic properties and an update on its therapeutic use with particular

reference to once-daily administration Drugs 35 604-645

4 Waxman DJ and Strominger JL (1983) Penicillin-binding proteins and the

mechanism of action of beta-lactam antibiotics Annu Rev Biochem 52(1) 825-869

5 Christ W (1991) properties of cephalosporines Infestion 19 244-252

6 Goonetilleke AK Dev D Aziz I Hughes C Smith MJ Basran GS (1996) A

comparative analysis of pharmacokinetics of ceftriaxone in serum and pleural fluid in

humans a study of once daily administration by intramuscular intravenous routes J

Antimicrob Chemother Dec 38(6) 969-76

7 Guerrini VH Filippich LJ Cao G R English PB Bourne DW (1985)

Pharmacokinetics of cefaronide ceftriaxone and cefperazone in sheep J Vet Pharmacol

Ther 8(2) 120-7

8 Swati Tiwari S Patel UD Bhavsar SK and Thaker AM (2010) Pharmacokinetics

and Bioavailability of Ceftriaxone in Patanwadi Sheep Online veterinary journal 5(2)

9 Ismail MM (2005) Pharmacokinetics urinary and mammary excretion of ceftriaxone in

lactating goats J Vet Med A Physiol Pathol Clin Med Sep 52(7) 354-8

10 Rajinder R prawez S Srivastiva AS (2005) Pharmacokinetics and dosage regimen of

ceftriaxone following its single ntramuscular adminsteration in kagani breed of goats

(Capra Hircus) Journal of reaserch 4(2) 91-93

11 Tiwari S Swati Bhavsar SK Patel UD and Thaker AM (2009) Disposition of

Ceftriaxone in Goats (Capra hircus) Online veterinary journal 4(2)

12 Dardi MS Sharma SK and Srivastava AK (2004) Pharmacokinetics and Dosage

regimen of ceftriaxone in buffalo calves Vet Res Commun 28 331-338

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

(739)[58]

for ceftazidime in a rabbit (966)[27]

for ceftriaxone in lactating goats (85)[9]

in lactating ewes (836)[25]

in domestic cats 8572[15]

for cefipime in goats 8645[47]

for ceftriaxone in buffulo calves 702[13]

and for ceftiofur in chickens 8890[37]

Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium

infected goats twics dialy for five days revealed that the drug could be detected in a

therapeutic level for 12hours following repeated intramuscular administrations and exceeded

the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]

The relative higher serum concentrations of ceftriaxone after the last dose compared to the

first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12

hours intervals for five consecutive days These observations agreed with data reported by[36]

on comparing the data of serum levels of repeated intramuscular injections with first

intramuscular injection it was revealed that repeated intramuscular injections of cefquinome

have cumulative effect in both species sheep and goats

The obtained result is inconsistent with that reported by[56]

who found thatwhen cefotaxime

was administered repetitively in patients the ratio of maximal serum levels after the last dose

to those after the first dose demonstrated minimal accumulation of intact drug and by[60]

who

found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in

buffalo calves

The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium

infected goats are significantly lower than those in normal goats following repeated

intramuscular injection These lower blood concentrations in Salmonella typhimurium

infected goats might be attributed to the higher penetrating power of ceftriaxone to the

diseased tissues[48]

This phenomenon is similar to data recorded by[61]

who suggested that

Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of

ceftriaxone These alterations might be due to fever and inflammation induced by

infections[59]

proved that the serum concentrations of cephradine following intramuscular

administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after

each intramuscular dose with a lower significant values recorded in Escherichia-coli infected

goats than in normal goatsAlso similer to that reported by[62]

who observed that the

maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep

wwwwjppscom Vol 5 Issue 01 2016

1451

Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

in comparison to normal sheepOn contrast[43]

reported that peak plasma level of cefotaxime

in febrile buffalo calves was higher than healthy buffalo calves

In this study the total body clearance (CLtot) in normal goats are significantly lower than in

Salmonella typhimurium infected goats This result supported by[61]

and[63]

fever and

inflammation are cardinal features in bacterial infection which may in turn caused an

increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all

these could lead to increased in the rate at which the drug was delivered to both organs which

were important sites of drug excretion This might somewhat explain the increase in the total

body clearance in infected goats This result is differ than that reported by[64]

who observed

that the clearance of ceftriaxone was significantly reduced in infected mice than in non

infected animals

The highest concentrations of ceftriaxone in milk are recorded 4 hours after each

intramuscular injection with a significant lower value in Salmonella typhimurium infected

goats than in normal goats This might be attributed to accumulation of drug in the inflammed

tissues[48]

This result is similar to those reported by[6559]

who found that milk concentrations

of gentamicin and cephradine were significantly lower in infected goats and cattle than in

normal ones respectively

The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the

non-ionic passive diffusion principle[66]

reported that most drug cross-lipid membranes by

passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly

influenced by the physicochemical properties of the drug[6768]

Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum

ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the

physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]

Milk

contains substantially more lipid and less protein than serum and is slightly more acidic

Therefore drugs which tend to concentrated in milk are weak bases with low serum protein

binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide

and aminothiazole also possesses an hydroxytriazinone group as new and additional

ionization center[70]

these compounds are sufficiently lipid- soluble to be able to penetrate

tissues

wwwwjppscom Vol 5 Issue 01 2016

1452

Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

The dose of ceftriaxone used in the present study induced therapeutically concentrations in

milk These concentrations suggested that ceftriaxone would be efficacious in treatment of

mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily

for 3-5 days

The study showed that the urine concentrations of ceftriaxone are greater than the concurrent

serum concentrations following intramuscular injection This observation is similar to those

reported in cows after cephapirin administrations[71]

In the present study urine concentrations of ceftriaxone increased with the repetition of

dosing This observation supported by[72]

after repeated intramuscular administrations of

ceftriaxone in healthy volunteeres

The mean peak urine concentrations of ceftriaxone were reached 2 hours after each

intramuscular injection The lower urine ceftriaxone concentrations in Salmonella

typhimurium infected goats than in normal goats might be attributed to the accumulation of

the drug in the inflamed tissues[48]

The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower

ratio in Salmonella typhimurium infected goats than in normal goats at different time of

sampling This indicates that glomerular filteration seemed to be the main pathway of

ceftriaxone elimination This observation supported by[59]

who found that the ratio between

cephradine clearance from blood of goats to creatinine clearance showed a marked decrease

in Escherichia-coli infected goats than in normal goats This indicated that glomerular

filteration seemed to be the main pathway of cephradine elimination with a limited rate of

tubular reabsorption

CONCLUSION

The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value

referred a better absorption of ceftriaxone from its site of intramuscular administration The

high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular

administrations suggested that ceftriaxone could be used for treatment of mastitis caused by

Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats

The high concentrations of ceftriaxone in urine after repeated intramuscular administrations

suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections

wwwwjppscom Vol 5 Issue 01 2016

1453

Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in

goats

REFERANCES

1 Neu HC Merpol NJ and Fukp (1981) Antibacterial activity of ceftriaxone

abetalactamase stable cephalosporines Antimicrobial agents and chemotherapy 19

414-423

2 Richard DM Heel RC Brogden RN Speight TM Avery GS (1984) Ceftriaxone a

review of its antibacterial activity pharmacological properties and therapeutic uses

Drugs 27 469-527

3 Brogden RN and Ward A (1988) Ceftriaxone a reappraisal of its antibacterial activity

and pharmacokinetic properties and an update on its therapeutic use with particular

reference to once-daily administration Drugs 35 604-645

4 Waxman DJ and Strominger JL (1983) Penicillin-binding proteins and the

mechanism of action of beta-lactam antibiotics Annu Rev Biochem 52(1) 825-869

5 Christ W (1991) properties of cephalosporines Infestion 19 244-252

6 Goonetilleke AK Dev D Aziz I Hughes C Smith MJ Basran GS (1996) A

comparative analysis of pharmacokinetics of ceftriaxone in serum and pleural fluid in

humans a study of once daily administration by intramuscular intravenous routes J

Antimicrob Chemother Dec 38(6) 969-76

7 Guerrini VH Filippich LJ Cao G R English PB Bourne DW (1985)

Pharmacokinetics of cefaronide ceftriaxone and cefperazone in sheep J Vet Pharmacol

Ther 8(2) 120-7

8 Swati Tiwari S Patel UD Bhavsar SK and Thaker AM (2010) Pharmacokinetics

and Bioavailability of Ceftriaxone in Patanwadi Sheep Online veterinary journal 5(2)

9 Ismail MM (2005) Pharmacokinetics urinary and mammary excretion of ceftriaxone in

lactating goats J Vet Med A Physiol Pathol Clin Med Sep 52(7) 354-8

10 Rajinder R prawez S Srivastiva AS (2005) Pharmacokinetics and dosage regimen of

ceftriaxone following its single ntramuscular adminsteration in kagani breed of goats

(Capra Hircus) Journal of reaserch 4(2) 91-93

11 Tiwari S Swati Bhavsar SK Patel UD and Thaker AM (2009) Disposition of

Ceftriaxone in Goats (Capra hircus) Online veterinary journal 4(2)

12 Dardi MS Sharma SK and Srivastava AK (2004) Pharmacokinetics and Dosage

regimen of ceftriaxone in buffalo calves Vet Res Commun 28 331-338

wwwwjppscom Vol 5 Issue 01 2016

1451

Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

in comparison to normal sheepOn contrast[43]

reported that peak plasma level of cefotaxime

in febrile buffalo calves was higher than healthy buffalo calves

In this study the total body clearance (CLtot) in normal goats are significantly lower than in

Salmonella typhimurium infected goats This result supported by[61]

and[63]

fever and

inflammation are cardinal features in bacterial infection which may in turn caused an

increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all

these could lead to increased in the rate at which the drug was delivered to both organs which

were important sites of drug excretion This might somewhat explain the increase in the total

body clearance in infected goats This result is differ than that reported by[64]

who observed

that the clearance of ceftriaxone was significantly reduced in infected mice than in non

infected animals

The highest concentrations of ceftriaxone in milk are recorded 4 hours after each

intramuscular injection with a significant lower value in Salmonella typhimurium infected

goats than in normal goats This might be attributed to accumulation of drug in the inflammed

tissues[48]

This result is similar to those reported by[6559]

who found that milk concentrations

of gentamicin and cephradine were significantly lower in infected goats and cattle than in

normal ones respectively

The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the

non-ionic passive diffusion principle[66]

reported that most drug cross-lipid membranes by

passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly

influenced by the physicochemical properties of the drug[6768]

Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum

ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the

physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]

Milk

contains substantially more lipid and less protein than serum and is slightly more acidic

Therefore drugs which tend to concentrated in milk are weak bases with low serum protein

binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide

and aminothiazole also possesses an hydroxytriazinone group as new and additional

ionization center[70]

these compounds are sufficiently lipid- soluble to be able to penetrate

tissues

wwwwjppscom Vol 5 Issue 01 2016

1452

Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

The dose of ceftriaxone used in the present study induced therapeutically concentrations in

milk These concentrations suggested that ceftriaxone would be efficacious in treatment of

mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily

for 3-5 days

The study showed that the urine concentrations of ceftriaxone are greater than the concurrent

serum concentrations following intramuscular injection This observation is similar to those

reported in cows after cephapirin administrations[71]

In the present study urine concentrations of ceftriaxone increased with the repetition of

dosing This observation supported by[72]

after repeated intramuscular administrations of

ceftriaxone in healthy volunteeres

The mean peak urine concentrations of ceftriaxone were reached 2 hours after each

intramuscular injection The lower urine ceftriaxone concentrations in Salmonella

typhimurium infected goats than in normal goats might be attributed to the accumulation of

the drug in the inflamed tissues[48]

The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower

ratio in Salmonella typhimurium infected goats than in normal goats at different time of

sampling This indicates that glomerular filteration seemed to be the main pathway of

ceftriaxone elimination This observation supported by[59]

who found that the ratio between

cephradine clearance from blood of goats to creatinine clearance showed a marked decrease

in Escherichia-coli infected goats than in normal goats This indicated that glomerular

filteration seemed to be the main pathway of cephradine elimination with a limited rate of

tubular reabsorption

CONCLUSION

The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value

referred a better absorption of ceftriaxone from its site of intramuscular administration The

high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular

administrations suggested that ceftriaxone could be used for treatment of mastitis caused by

Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats

The high concentrations of ceftriaxone in urine after repeated intramuscular administrations

suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections

wwwwjppscom Vol 5 Issue 01 2016

1453

Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in

goats

REFERANCES

1 Neu HC Merpol NJ and Fukp (1981) Antibacterial activity of ceftriaxone

abetalactamase stable cephalosporines Antimicrobial agents and chemotherapy 19

414-423

2 Richard DM Heel RC Brogden RN Speight TM Avery GS (1984) Ceftriaxone a

review of its antibacterial activity pharmacological properties and therapeutic uses

Drugs 27 469-527

3 Brogden RN and Ward A (1988) Ceftriaxone a reappraisal of its antibacterial activity

and pharmacokinetic properties and an update on its therapeutic use with particular

reference to once-daily administration Drugs 35 604-645

4 Waxman DJ and Strominger JL (1983) Penicillin-binding proteins and the

mechanism of action of beta-lactam antibiotics Annu Rev Biochem 52(1) 825-869

5 Christ W (1991) properties of cephalosporines Infestion 19 244-252

6 Goonetilleke AK Dev D Aziz I Hughes C Smith MJ Basran GS (1996) A

comparative analysis of pharmacokinetics of ceftriaxone in serum and pleural fluid in

humans a study of once daily administration by intramuscular intravenous routes J

Antimicrob Chemother Dec 38(6) 969-76

7 Guerrini VH Filippich LJ Cao G R English PB Bourne DW (1985)

Pharmacokinetics of cefaronide ceftriaxone and cefperazone in sheep J Vet Pharmacol

Ther 8(2) 120-7

8 Swati Tiwari S Patel UD Bhavsar SK and Thaker AM (2010) Pharmacokinetics

and Bioavailability of Ceftriaxone in Patanwadi Sheep Online veterinary journal 5(2)

9 Ismail MM (2005) Pharmacokinetics urinary and mammary excretion of ceftriaxone in

lactating goats J Vet Med A Physiol Pathol Clin Med Sep 52(7) 354-8

10 Rajinder R prawez S Srivastiva AS (2005) Pharmacokinetics and dosage regimen of

ceftriaxone following its single ntramuscular adminsteration in kagani breed of goats

(Capra Hircus) Journal of reaserch 4(2) 91-93

11 Tiwari S Swati Bhavsar SK Patel UD and Thaker AM (2009) Disposition of

Ceftriaxone in Goats (Capra hircus) Online veterinary journal 4(2)

12 Dardi MS Sharma SK and Srivastava AK (2004) Pharmacokinetics and Dosage

regimen of ceftriaxone in buffalo calves Vet Res Commun 28 331-338

wwwwjppscom Vol 5 Issue 01 2016

1452

Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

The dose of ceftriaxone used in the present study induced therapeutically concentrations in

milk These concentrations suggested that ceftriaxone would be efficacious in treatment of

mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily

for 3-5 days

The study showed that the urine concentrations of ceftriaxone are greater than the concurrent

serum concentrations following intramuscular injection This observation is similar to those

reported in cows after cephapirin administrations[71]

In the present study urine concentrations of ceftriaxone increased with the repetition of

dosing This observation supported by[72]

after repeated intramuscular administrations of

ceftriaxone in healthy volunteeres

The mean peak urine concentrations of ceftriaxone were reached 2 hours after each

intramuscular injection The lower urine ceftriaxone concentrations in Salmonella

typhimurium infected goats than in normal goats might be attributed to the accumulation of

the drug in the inflamed tissues[48]

The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower

ratio in Salmonella typhimurium infected goats than in normal goats at different time of

sampling This indicates that glomerular filteration seemed to be the main pathway of

ceftriaxone elimination This observation supported by[59]

who found that the ratio between

cephradine clearance from blood of goats to creatinine clearance showed a marked decrease

in Escherichia-coli infected goats than in normal goats This indicated that glomerular

filteration seemed to be the main pathway of cephradine elimination with a limited rate of

tubular reabsorption

CONCLUSION

The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value

referred a better absorption of ceftriaxone from its site of intramuscular administration The

high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular

administrations suggested that ceftriaxone could be used for treatment of mastitis caused by

Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats

The high concentrations of ceftriaxone in urine after repeated intramuscular administrations

suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections

wwwwjppscom Vol 5 Issue 01 2016

1453

Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in

goats

REFERANCES

1 Neu HC Merpol NJ and Fukp (1981) Antibacterial activity of ceftriaxone

abetalactamase stable cephalosporines Antimicrobial agents and chemotherapy 19

414-423

2 Richard DM Heel RC Brogden RN Speight TM Avery GS (1984) Ceftriaxone a

review of its antibacterial activity pharmacological properties and therapeutic uses

Drugs 27 469-527

3 Brogden RN and Ward A (1988) Ceftriaxone a reappraisal of its antibacterial activity

and pharmacokinetic properties and an update on its therapeutic use with particular

reference to once-daily administration Drugs 35 604-645

4 Waxman DJ and Strominger JL (1983) Penicillin-binding proteins and the

mechanism of action of beta-lactam antibiotics Annu Rev Biochem 52(1) 825-869

5 Christ W (1991) properties of cephalosporines Infestion 19 244-252

6 Goonetilleke AK Dev D Aziz I Hughes C Smith MJ Basran GS (1996) A

comparative analysis of pharmacokinetics of ceftriaxone in serum and pleural fluid in

humans a study of once daily administration by intramuscular intravenous routes J

Antimicrob Chemother Dec 38(6) 969-76

7 Guerrini VH Filippich LJ Cao G R English PB Bourne DW (1985)

Pharmacokinetics of cefaronide ceftriaxone and cefperazone in sheep J Vet Pharmacol

Ther 8(2) 120-7

8 Swati Tiwari S Patel UD Bhavsar SK and Thaker AM (2010) Pharmacokinetics

and Bioavailability of Ceftriaxone in Patanwadi Sheep Online veterinary journal 5(2)

9 Ismail MM (2005) Pharmacokinetics urinary and mammary excretion of ceftriaxone in

lactating goats J Vet Med A Physiol Pathol Clin Med Sep 52(7) 354-8

10 Rajinder R prawez S Srivastiva AS (2005) Pharmacokinetics and dosage regimen of

ceftriaxone following its single ntramuscular adminsteration in kagani breed of goats

(Capra Hircus) Journal of reaserch 4(2) 91-93

11 Tiwari S Swati Bhavsar SK Patel UD and Thaker AM (2009) Disposition of

Ceftriaxone in Goats (Capra hircus) Online veterinary journal 4(2)

12 Dardi MS Sharma SK and Srivastava AK (2004) Pharmacokinetics and Dosage

regimen of ceftriaxone in buffalo calves Vet Res Commun 28 331-338

wwwwjppscom Vol 5 Issue 01 2016

1453

Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in

goats

REFERANCES

1 Neu HC Merpol NJ and Fukp (1981) Antibacterial activity of ceftriaxone

abetalactamase stable cephalosporines Antimicrobial agents and chemotherapy 19

414-423

2 Richard DM Heel RC Brogden RN Speight TM Avery GS (1984) Ceftriaxone a

review of its antibacterial activity pharmacological properties and therapeutic uses

Drugs 27 469-527

3 Brogden RN and Ward A (1988) Ceftriaxone a reappraisal of its antibacterial activity

and pharmacokinetic properties and an update on its therapeutic use with particular

reference to once-daily administration Drugs 35 604-645

4 Waxman DJ and Strominger JL (1983) Penicillin-binding proteins and the

mechanism of action of beta-lactam antibiotics Annu Rev Biochem 52(1) 825-869

5 Christ W (1991) properties of cephalosporines Infestion 19 244-252

6 Goonetilleke AK Dev D Aziz I Hughes C Smith MJ Basran GS (1996) A

comparative analysis of pharmacokinetics of ceftriaxone in serum and pleural fluid in

humans a study of once daily administration by intramuscular intravenous routes J

Antimicrob Chemother Dec 38(6) 969-76

7 Guerrini VH Filippich LJ Cao G R English PB Bourne DW (1985)

Pharmacokinetics of cefaronide ceftriaxone and cefperazone in sheep J Vet Pharmacol

Ther 8(2) 120-7

8 Swati Tiwari S Patel UD Bhavsar SK and Thaker AM (2010) Pharmacokinetics

and Bioavailability of Ceftriaxone in Patanwadi Sheep Online veterinary journal 5(2)

9 Ismail MM (2005) Pharmacokinetics urinary and mammary excretion of ceftriaxone in

lactating goats J Vet Med A Physiol Pathol Clin Med Sep 52(7) 354-8

10 Rajinder R prawez S Srivastiva AS (2005) Pharmacokinetics and dosage regimen of

ceftriaxone following its single ntramuscular adminsteration in kagani breed of goats

(Capra Hircus) Journal of reaserch 4(2) 91-93

11 Tiwari S Swati Bhavsar SK Patel UD and Thaker AM (2009) Disposition of

Ceftriaxone in Goats (Capra hircus) Online veterinary journal 4(2)

12 Dardi MS Sharma SK and Srivastava AK (2004) Pharmacokinetics and Dosage

regimen of ceftriaxone in buffalo calves Vet Res Commun 28 331-338

wwwwjppscom Vol 5 Issue 01 2016

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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences

13 Gohil P V Patel U D Bhavsar S K Thaker A M (2009) Pharmacokinetics of

ceftriaxone in buffalo calves (Bubalus bubalis) following intravenous and intramuscular

administration Iranian Journal of Veterinary Research 10(1) 33-37

14 Maradyia JJ Harshad VG Shaliesh KB Urvesh DP Aswin MT (2010)

Pharmacokinetics of ceftriaxone in calves Veterinarski arhiv 80(1) 1-9 2010

15 Albarellos GA Kreil VE Landoni MF (2007) Pharmacokinetics of ceftriaxone after

intravenous intramuscular and subcutaneous administration to domestic cats J Vet

Pharmacol Ther Aug 30(4) 345-52

16 Johal B and Srivastava AK (1998) Pharmacokinetics urinary excretion and dosage

regimen of ceftriaxone in Crossbred cow calves 68(10)

17 Otesile EB Ahmed G and Adetosoye AI (1990) Experimental infection of Red Sokoto

goats with Salmonella typhimurium Rev Eacutelev Meacuted Veacutet Pays trop 43(1) 49-53

18 Iroha I R Amadi E S Orji JO and Esimone C O (2008) In vitro evaluation of the

activity of colloidal silver concentrate against Pseudomonas aeruginosa isolated from

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19 Bennett JV Brodie JL Benner E and Kibry W (1966) Simplified accurate method

for antibiotic assay for clinical specimen Appl Microbial 14 170-175

20 Grove DC and Randall WA (1955) Assay methods of antibiotics Medical

encyclopedia New York 79(12) 259-32

21 Murray R (1984) Creatinin kaplane et al Clinc Chem Ther CV Mosby Co S Louis

Toronto Princeton 1261-1266 and 418

22 Baggot JD (1978a) Some aspect of clinical pharmacokinetics in veterinary medicine I J

Vet Pharm Ther 1 5-18

23 Baggot JD (1978b) Some aspect of clinical pharmacokinetics in veterinary medicine II

J Vet Pharm Ther 1 111-118

24 Snedecor GW and Cokran WG (1980) Statistical method 7th

Ed The Iowa state

university press Ames Iowa USA 39-63

25 Goudah A Shin HC Shim JH Abd El-Aty AM (2006) Characterization of the

relationship between serum and milk residu disposition of ceftriaxone in lactating ewe J

Vet Pharmacol Ther Aug 29(4) 307-12

26 Jayesh J M Harshad V G Shailesh K B Urvesh D P and Aswin M T (2010)

Pharmacokinetics of ceftriaxone in calves Veterinarski arshiv 80(1) 1-9

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27 Abd-El-Aty AM Goudah A and Abo E S K (2001) Pharmacokinetics

intramuscular bioavailability and tissue residue profiles of ceftazidime in a rabbit

model Dtsch Tierarztl Wochenschr 108(4) 168-171

28 Gardner S Y and Papich M G (2001) Comparison of cefepime pharmacokinetics in

neonatal foals and adult dogs J Vet Pharmacol Therap 24(3) 187-192

29 Ismail M (2005a) Pharmacokinetics of cefepime administered by iv and im routes to

ewes J Vet Pharmacol Therap 28(6) 499-503

30 Patel U D Bhavsar S K and Thaker A M (2006) Pharmacokinetics and dosage

regimen of cefepime following single dose intravenous administration in calves Iran J

Pharmacol Therapeut 5(2) 127-130

31 El-Gendy AAM Tohamy MA and Ismail M (2007) Comparative pharmacokinetic

and renal clearance study of ceftiofur in cross breed friesian and buffalo calves BS Vet

Med J 17(1) 69-77

32 Joshi B and Kumar Sharma S (2009) The pharmacokinetics of cefepime in E coli

lipopolysaccharide induced febrile buffalo calves Veterinarski arhiv 79(6) 523-530

33 Tohamy MA (2008) Pharmacokinetics of ceftiofur sodium administered concomitantly

with dipyrone in healthy and feverish cows J Egypt Soc Pharmacol Exp Ther 29(2)

10-15

34 Rajput N Kumar V D and Sandhu HS (2011) Pharmacokinetics and dosage

regimen of cefpirome in febrile cross-bred calves Iran J Pharmacol Ther 10(1) 17-20

35 Abo-El- Sooud K and Tohamy MA (2011) Comparative pharmacokinetics and milk

concentrations of ceftazidime in healthy and mastitic goats Insight Pharmaceut Sci

1(1) 11-17

36 El-Hewaity M Abd El Latif A Soliman A and Aboubakr M (2014) Comparative

pharmacokinetics of cefquinome (Cobactan 25) following repeated intramuscular

administrations in sheep and goats J Vet Med Doi 949642 1-5

37 El-Sayed M G A El-Komy A A A El barawy A M and Ibrahim D M A (2015)

Pharmacokinetics and tissue residues of ceftiofur in normal and Escherichia coli infected

chickens J Phys Pharm Adv 5(3) 574-582

38 Datta B Mandal TK and Chakraborty A K (2003) Pharmacokinetics of cefotaxime

in goats with experimentally induced kidney damage Ind J pharmacol (35) 173-176

39 Guerrini HV English BP Filippich J L Schneider J and Bourne D W (1986)

The pharmacokinetics of cefotaxime in dog Vet Rec 119(4) 81-83

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40 Atef M Ramadan A Afifi N A and Youssef S A (1990) pharmacokinetic profile

of cefotaxime in goat Res Vet Sci 49(1) 34-38

41 Satish K G Chaudhary RK Srivastiva AK and Garg BD (1990) Pharmacokintics

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intravenous and intramusculer adminsteration Veterinary research commuincation 14

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42 Goudah A (2008) Pharmacokinetic parameters of ceftriaxone after single intravenous

and intramuscular administration in camels (Camelus Dromedarius) Res Vet Sci Jun

84(3) 483-9

43 Sharma SK Srivastava AK and Deore DM (2006) Effect of Ecoli

lipopolysaccharides ndashinduced fever on disposition pattern of cefotaxime in buffalo calves

Veterinarski Arhiv 76(6) 537-545

44 Baggot JD (1977) Priniciple of pharmacokinetics In principle of drug disposition in

domestic animals The physiological Basis of veterinary Clinical Pharmacology 1st ed

WB Saunders Co Philadelphi PA 168-179

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