11 FARMAKOKINETIKA KLINIK ANTIBIOTIKA AMINOGLIKOSIDA.pdf

8/9/2019 11 FARMAKOKINETIKA KLINIK ANTIBIOTIKA AMINOGLIKOSIDA.pdf

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FARMAKOKINETIKA KLINIK

ANTIBIOTIKA AMINOGLIKOSIDA

Arief Rahman Hakim

[email protected]

PENDAHULUAN

Aminoglikosida :

Bactericidal, treatment serious gram-negativeinfections

Absorption from GI is poorparenterally (byintermittent iv infusion)

Pemilihan dosis dipengaruhi oleh : specific agent (sptgentamicin vs amikacin), infection (spt site andorganism), renal function, dan weight or bodycomposition patient

Most commonly monitored : gentamicin, tobramycin,and amikacin


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PENDAHULUAN

Usual dose :

Gentamicin and tobramycin : 50-120 mg (1-2

mg/kg), diberikan selama 30-60 menit dengan

interval dosis tiap 8 jam

Amikacin : 200-500 mg (5-7,5 mg/kg) tiap 8-12

jam

Cl, Vd, t1/2similar, model farmakokinetika

yang sama dapat digunakan untuk semua

aminoglikosida


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KONSENTRASI PLASMA TERAPETIK &

TOKSIK

Peak Cp (Cpss max) gentamicin & tobramycin : 4-8 mg/L Cp


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BIOAVAILABILITAS (F)

Antibiotika aminoglikosidavery water

soluble and poorly lipid soluble

Poorly absorbed when administered orally and

must be administered parenterally for the

treatment of systemic infections

F = 1

S = 1

VOLUME DISTRIBUSI (Vd)

Vd = 0,25 L/kg, relatively wide range 0,1-0,5

L/kg reported

Vd untuk pasien obese = (0,25 L/kg)(IBW) +

0,1 (TBW-IBW)

Vd increased in patient with ascites, edema, orother enlarged third space volume

AsumsiVd approximately equal to the

extracelluar fluid volume


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VOLUME DISTRIBUSI (Vd)

Vd untuk pasien dengan third space volume

Vd (L) = (0,25 L/kg *non-obese, non-excess fluid weight(kg)) + 0,1*(excess adipose weight (kg)) + (excess thirdspace fluid weight (kg)

Non-obese, non-excess fluid weight = IBW

Excess adipose weight = TBW-IBW (tanpa excess third-spacefluid)

Excess third-space fluid weight = difference between theinitial and current weight

One-compartment model is generally assumedfor aminoglikosida farmakokineka calculation

Klirens (Cl)

Eliminasi aminoglikosida almost entirely by therenal route

Since aminoglikosida and ClCrare similar over awide range of renal function, Cl aminoglikosidacan be estimated from the formula used toestimate ClCrwhen Cp within the therapeutic

range Correct estimate of ClCrcan only be obtained if

the patients weight represents a normal ratio ofmuscle mass to TBW, and serum creatinine atsteady state


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Klirens (Cl)

Cl untuk morbidly obese (BB = 2*IBW) BB = IBW + 0,4*(TBW-IBW)

Another factor which should be considered whenestimating Cl aminoglikosidanon-renal Cl =0,0021 L/kg/jam (= 2,5 mL/menit/70 kg)

Non-renal Cl generally ignored in most patient,but it significant in patient whose renal functionis markedly diminished

Anephric and on intermittent hemodialysis patient

Cl = 0,0043 L/kg/jam (5 mL/menit/70 kg) representsthe residual renal klirens as well as non-renal klirens

Klirens (Cl)

Carbenicillin, ticarcillin, and related extended spectrumpenicillins inactivate gentamicin and tobramycin invitro

Clinically significant in vivo in patients with renal failure

This interaction function of the specific aminoglikosida, thepenicillin compound, the concentration of the penicillin

compound, and temperature

Amikacin much less likely to interact with thesepenicillins

Cl Tobramycin, Gentamicin by Carbenicillin (L/jam) =(0,017/jam)*(Vd aminoglikosida)


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WAKTU PARO ELIMINASI (t1/2)

/2=0,693

Since renal function varies considerably amongindividuals, t1/2also variable

Contoh : Pria, 70 kg, 25 tahun dengan SCr0,8 mg/dLCl

aminoglikosida = 100 mL/menit, bila Vd 0,25 L/kgt1/2=2 jam

Pria, 75 tahun, Vd sama, SCr1,4 mg/dLCl aminoglikosida= 35 mL/menit, t1/2= 6 jam

Initial aminoglikosida dose and dosing interval shouldbe selected with care


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TIME TO SAMPLE

Correct timing of the sample collectionimportant, because aminoglikosida have arelatively short half-life and small but significantdistribustion phase

Peak Cp be obtained one hour after the DMinitiated, assume drug infused over about 30minutes (acceptable the infusion period 20-40minutes)

Trough Cp should be obtained within the half-hour (setengah jam) before the administration ofthe next DM

TIME TO SAMPLE

Cp clinical peak which one hour after start infusion :

0 =

Optimal time to sample within first 24 hours therapydifficult to determine

Standard practice to obtain the first aminoglikosida

sample after three or four doses administered,majority patient approching steady state by this time.

When aminoglikosida administered IM, time aborptionless predictable; Cp max about one hour after IMinjectionCp max should be obtained in this time


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PERSAMAAN

When duration infusion or absorption less

than one-sixth of half-live (1/2*t1/2)the short infusion

model used :

Cp2=

( 1 )()


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PERSAMAAN

In patient with decreased renal function and

longer aminoglikosida half-livebolus dose

model could be used satifactory

In patient with good renal function (yi young

adults and children), use infusion model is

more appropriate, because have very short

aminoglikosida half-live

PERSAMAAN

If bolus dose model applied, used to predict

the peak levels steady state :

=

()

t1= time interval between start infusion and time

at peak concentration sample

= interval between dose


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PERSAMAAN

Trough concentration (Cpss min) at steady

state :

Cpss min =

()

= interval between dose

PERSAMAAN

If infusion model used :

=

( 1 )

tin= duration infusion


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PERSAMAAN

Intermittent infusion steady state model :

Cpss2 =

= dosing interval,

t2 = time interval between the end infusion and

time at concentration measured

PERSAMAAN

Intermittent infusion steady state model

trough concentration at steady state :

Cpss min =

()

= dosing interval,

t2 = time interval between the end infusion and

time at concentration measured = -tin


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TUGAS KELOMPOK

Kirimkan email ke [email protected] mintamateri kuliah dan tugas kelompok dengan menyebutnama, no mhs, kelompok berapa dan FKK berapa

Analisis kasus-kasus berikut, bagilah untuk semuaanggota kelompoknya

Laporan kelompok dikirimkan via email denganmemberikan nama file laporan : kelompok berapa FKKberapa

Laporan kelompok diserahkan paling lambat hari Kamistanggal 18 Desember 2014 pukul 23:59:59 WIB

Kasus 1

R.W., 30 tahun, 70 kg, wanita dengan serumkreatinin 0,9 mg/dL. Diberikan gentamicindengan dosis awal 100 mg secara infus ivselama 30 menit. Hitunglah konsentrasiplasma gentamicin 1 jam setelah infus iv

dimulai. Bila gentamisin diberikan tiap 8 jam, hitunglah

konsentrasi tunak plasma maksimum danminimum gentamisin
mailto:[email protected]:[email protected]


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Kasus 2

L.K., 40 tahun, 50 kg, wanita dengan serum kreatinin 1mg/dL diberikan tobramycin. Tentukan dosispemeliharaan dan interval dosis tobramycin yang dapatmenghasilkan konsentrasi maksimum tunak 7 mg/Lsatu jam setelah infus iv dimulai dan konsentrasiminimum tunak


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Kasus 4

D.H., 40 tahun, pria dibawa ke UGD. Pasienmemiliki tinggi badan 165 cm dan saat masukUGM BB 85 kg. Pasien akan menjalani operasiabdominal dan setelah operasi mengalamihipotensi dan diberikan cairan infus denganvolum besar untuk menjaga tekanan darahnya.Saat ini, BB nya 105 kg dan serum kreatininnya 2mg/dL. D.H. Menerima gentamicin sebagai terapiempiris paska operasi abdominal.

Rekomendasikan regimen dosis gentamisin agardapat menghasilkan konsentrasi tunakmaksimum 5-7 mg/L dan minimum


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Kasus 6

T.C. Diberikan tobramycin 120 mg secara infus

iv selama 30 menit tiap 8 jam, yaitu pada jam

1:00, 9:00, dan 17:00. Konsentrasi tunak

tobramycin diukur pada jam 8:30 dan 11:30

dihasilkan kadarnya berturut-turut 0,9 mg/L

dan 3,9 mg/L. Hitunglah konsentrasi tunak

maksimal tobramycin pada jam 10:00 (satu

jam setelah infus dimulai).

11 FARMAKOKINETIKA KLINIK ANTIBIOTIKA AMINOGLIKOSIDA.pdf

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