2. Final Pharmacokinetics Workshop (Consized)-1

7/28/2019 2. Final Pharmacokinetics Workshop (Consized)-1

1/17

Pharmacokinetics workshop

MohammedEl-SakkarMSc (Pediatrics), MD, PhD (Pharmacology)

Allergy & Immunology consultantProfessor of Pharmacology

University of Alexandria

2013


2/17

If a patient taking 0.25 mg tablet of digoxin daily, requires IV

administration of the drug.

What would an equivalent dose be? When F for tablet is 0.62.

F for I.V. doses is 1

F for tablet is 0.62

Amount reach to circulation intact = 0.25 X 0.62 = 0.155 mg

I.V. dose = 0.155 mg

Amount reach to systemic circulation intact = Dose (extravascular) X F


3/17

What is the equivalent dosage of oral theophylline for a patient

receiving IV aminophylline at a rate of 80 mg/hr?

N.B theophylline is completely absorbed on oral administrationand 80% of aminophylline weight is theophylline.

I.V. aminophylline dose per day= 80 x 24 = 1920 mg/day

TheophyllineAminophylline

80100

?1920

Oral theophylline dose = 1920x 80 = 1536 mg/day

100


4/17

A normal volunteer will receive a new drug in a phase I clinical

trial. The clearance and volume of distribution of the drug in

this subject are 1.386 L/h and 80 L, respectively. The half life

of the drug in this subject will be approximately

t =Cl

0.693 X Vd

t

= 1.386 L/h

0.693 X 80 L

= 40 h

Cl = 1.386 L/h Vd = 80 L


5/17

Estimate the oral loading dose of digoxin for a 70 kg man, which

would be necessary to attain a plasma level of 1.5 g/L

(microgram/L)? Vd of digoxin is reduced to 420 L, F for tablet is0.62

Loading dose=X Desired initial plasma concentration (amount/vol)Vd

Bioavailability (F)

420 (L) X 1.5 g/L

0.62= 1016 g


6/17

What is the apparent clearance of lidocaine in a patient who is

receiving an IV infusion of 2 mg/min and has a steady state

plasma level of 3 mg/L? (Given is: Vd = 7.3 L/Kg and F = 0.7)

Maintenance dosing rate =

(amount/time)

X Cl (vol/time)Desired Plasma drug concentration ss

(Cpss)

Bioavailability (F)

= 40 L/h

Clearance (Cl) =Maintenance dosing rate x F

Cpss

120 mg/h

3 mg/L=

Clearance (Cl) =120 mg/h x 1

3 mg/L

120 mg/h

3 mg/L=


7/17

Alia is a 70 year-old 68 kg with CHF and chronic renal failure

(Clcr25ml/min). It is decided that a loading dose of digoxin is to

be administered orally. What must you consider in calculating

the estimated loading dose? The desired Cp is 1.5 microgram/L,Vd of digoxin is reduced to 4.7L/kg, F for tablet is 0.62

Loading dose=X Desired initial plasma concentration (amount/vol)Vd

Bioavailability (F)

4.7 L x 68 kg X 1.5 g/L

0.62 = 773g

Corrected dose = Average dosePatients creatinine clearance

100 mL/minX

Corrected dose in RF = 773 gX

25

100 = 193.25 g


8/17


9/17

What will be an appropriate maintenance infusion rate of

aminophylline to keep the plasma level at 15 mcg/ml? The

clearance of theophylline in arithmetic adults is 4.73L/hr

Maintenance dosing rate =

(amount/time)

X Cl(vol/time)Cpss

Bioavailability (F)

15 mg/L X 4.73L/hr

1 = 70.95 mg/h theophylline

Aminophylline maintemance dose = 70.95 x 100/80 = 88.6 mg/h


10/17

Loading dose =Vd x Target concentration

Bioavailability (F)

A 70 kg patient states she ingested approximately 30 tablets of

phenobarbitone each contain 100mg. Vd listed is 0.75 L/kg. Peak

blood concentration measured by the lab is 60 mg/L, F=1. How

can you verify the history?

0.75 x 70x 60

1= 3150 mg=

= 3000 mg

The history is correct

She say 30x 100 =


11/17


Bioavailability (F)

A 70 kg patient states she ingested approximately 30 tablets of

phenobarbitone each contain 100mg. Vd listed is 0.75 L/kg. Peak

blood concentration measured by the lab is 60 mg/L, F=1. How

can you verify the history?

Target concentration =LD x F

Vd

3000 x 1

0.75 x 70= 57 mg/L=

The history is correct


12/17

A 70 kg patient ingested an unknown number of lithium cap (300

mg = 8 mEq) and has a peak concentration of 5 mEq/L . The

patient is now agitated. What is the number of capsules

ingested? Its Vd is 0.7L/kg, F=1.


Bioavailability (F)

(0.7 x 70) x 5 mEq/L = 245 mEq

Number of capsules ingested = 245 mEq8 mEq

= 30 cap of 300 mg


13/17

Despite your careful adherence to basic pharmacokinetic

principles, your patient on digoxin therapy has developed

digitalis toxicity. The plasma digoxin level is 4 ng/mL. Renal

function is normal, and the plasma t for digoxin in thispatient is 1.6 days. How long should you withhold digoxin in

order to reach a safer yet probably therapeutic level of 1

ng/mL?

Since the blood level for a drug with first-order kinetics drops by 50%

during each half-life, the level will be 2 ng/mL after 1.6 days and 1 ng/mL

after 3.2 days.

0 2 64 8 2 64 8 100

25

75

50

100

%

ofmaximum

Time (number of half-lives)

Start

infusion

Stop

infusion


14/17

A new drug was studied in 20 healthy volunteers to determine basic

pharmacokinetic parameters. A dose of 100 mg was administered as an

intravenous bolus to each volunteer and blood samples were analyzed at

intervals as shown in the graph below. The average plasma concentrations

at each time are shown by the solid circles at 10 and 30 minutes and at 1,

2, 3, 4, 6, and 8 hours after administration.

Determine :

Elimination half life

Vd

Clearance


15/17

The elimination phase of the graph of plasma concentration follows a

straight line on the semi logarithmic graph, so we can conclude that the

new drug follows first-order kinetics, the first requirement for determining

the half-life.The straight-line portion of the graph shows a decline of 50% from the 2-

hour point (4 mglL) to the 8-hour sample (2 mglL).

Half-life = 8 hs minus 2 hours = 6 hours.

Loading doseVd =

X Bioavailability (F)

Target concentration (Cp0)

100 mg x 1

5 mg/L= 20 L


16/17

t =Cl

0.693 X Vd

tCl = 0.693 X Vd

6 hCl =

0.693 X 20L= 2.3 L/h


17/17

2. Final Pharmacokinetics Workshop (Consized)-1

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