Pharmacokinetic Exercises list

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Pharmacokinetic Exercises list

© All Rights Reserved

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PHARMACOKINETIC PROBLEMS

EXERCISE 1

A 40-year old male patient (body weight 72 kg) has a serum creatinine of 4 mg/dL. He has

Proteus mirabilis-induced urinary tract infection sensitive only to gentamicin. Calculate the

gentamicin dose, which should be administered to this patient, presuming a gentamicin

dose of 5 mg/kg once a day for a patient with normal renal function. (Literature tells you that

in patients with normal renal function, renal clearance of gentamicin is 78 ml/minute and its

non-renal clearance is 3 ml/minute).

EXERCISE 2

If extraction ratio of a drug is 1.0, and hepatic blood flow is 1500 ml/min, what will be the

clearance (hepatic) for this drug?

EXERCISE 3

Hepatic first pass extraction of drug A is doubled from 2% to 4%, while for drug B it increases

from 90% to 95%, by an enzyme-inducing drug C. Assuming complete absorption from the

gut, bioavailability of which drug will be significantly altered by C?

EXERCISE 4

A patient is on maintenance dose of digoxin 0.25mg/day by oral route. Calculate the C ss

presuming normal renal function (Digoxin clearance 9 L/hr). If the maintenance dose is

increased to 0.375mg/day, calculate the new Css and the time required for the same.

EXERCISE 5

According to the prescribing information, following IV administration of cimetidine, 75% of

the drug is recovered from the urine after 24 hours as the parent compound. Following a

single oral dose, 48% of the drug is recovered from the urine after 24 hours as the parent

compound. From this information, what is the fraction of drug absorbed systemically from

the oral dose?

EXERCISE 6

The kidney actively secretes a new antibiotic and the apparent Vd is 3.5 liters in the normal

adult. The clearance of this drug is 650 ml/min.

a. What is the t1/2 for this drug?

b. What would be the new t1/2 for this drug in an adult with partial renal failure whose

clearance of the antibiotic is only 75 ml/min?

EXERCISE 7

Theophylline is effective in the treatment of bronchitis at a blood level of 10-20 mcg/ml. At

therapeutic range, theophylline follows first order kinetics. The average t1/2 is 3.4 hr and the

range is 1.8 - 6.8 hr. The average volume of distribution is 30 liters.

a. What are the average, upper and lower clearance limits for theophylline?

b. The renal clearance (Clr) of theophylline is 0.36 liter/hr. What is the Km and Ke

assuming all non-renal clearance (Clnr) is due to metabolism?

Km = metabolism rate constant

Ke = renal excretion rate constant

Pharmacokinetic Calculations and Exercises

EXERCISE 8

A drug has oral bioavailability of 80% when administered at a dose of 200 mg every 12 hourly

in a 70 kg man and has a total body clearance value of 120 ml/kg/hour. What is the steady

state concentration (Css) of the drug?

EXERCISE 9

Calculate the loading dose for a drug given by IV route that has long t 1/2 where goal is to

achieve plasma concentration of 1.2 mg/dl. The Vd at steady state (Vss) is 40 liters.

EXERCISE NO 10

Calculate the daily dose of Gentamicin for a 60 yr old woman with 60 kg body wt with serum

creatinine level 3mg/100ml.

EXERCISE NO 11

Calculate the loading & maintenance dose of lithium to maintain a steady state therapeutic

plasma conc. of 1.0 mEq/ litre.

EXERCISE NO 12

Calculate the loading and maintenance dose dioxin for a patient with low-output cardiac

failure with atrial fibrillation, to achieve the desired study state therapeutic concentration of

~ 1 ng/ml.

EXERCISE NO 13

A patient is given a rapid IV infusion of one liter of normal saline.

a. What would be the rise in plasma volume and sodium concentration?

b. Calculate the amount of sodium chloride to correct the hyponaetremia if the plasma

sodium level is 120mEq/liter.

EXERCISE NO 14

A patient developed digoxin toxicity with the plasma level of 4 ng/mL. The renal function

was normal. Presuming that half life of digoxin is 40 hours, how long digoxin has to be

withhold to reach a safer therapeutic level of 1 ng/mL?

EXERCISE NO 15

Verapamil and phenytoin are eliminated from the body by hepatic metabolism with the

clearance rate of 1.5 L/min and 0.1 L/min respectively. When these drugs are administered

along with rifampicin, what is the consequent effect on the clearance of each of these

drugs?

EXERCISE NO 16

A 60-year-old man is hospitalized due to MI with severe ventricular arrhythmia. He is started

with an anti-arrhythmic drug with a relatively narrow margin of safety with minimum toxic

plasma concentration 1.5 times the minimum therapeutic plasma concentration. The half life

of the drug is 6 hours. To maintain the therapeutic concentration above the minimum

required, what should be the pattern of administration?

Pharmacokinetic Calculations and Exercises

EXERCISE NO 17

A 50-year-old woman with metastatic breast cancer is given a chemotherapeutic agent at a

constant IV infusion of 8 mg/hour. If the V d is 30 liters, clearance 2 liters/hour, what would be

the steady state therapeutic concentration after 40 hours if the infusion rate is doubled?

EXERCISE NO 18

A young man is brought to the emergency in deep coma. It was learnt by his housemates

that he had self-administered a large of morphine 6 hours earlier. An immediate blood

analysis showed the morphine blood level of 0.2 mg/liter. Presuming the volume of

distribution as 200 liters and half life of 3 hours, how much of morphine did the patient inject

6 hours earlier?

EXERCISE NO 19

A patient is started with an IV infusion of procainamide at 9 AM. The blood concentration

measured at 1 PM was 3 mg/mL. What would be the steady state concentration after 12

hours of infusion? ( t1/2 of procainamide=2hrs)

EXERCISE NO 20

A healthy human volunteer has received a new drug during a phase I clinical trial. The

clearance rate and volume of distribution of the drug are 1.386 L/hour and 80 liters

respectively. Calculate the half life of the drug in the subject.

EXERCISE NO 21

A 19-year-old woman hospitalized due to severe asthmatic wheezing is started with IV

infusion of theophylline. If the infusion of theophylline is started at the rate of 0.48 mg/min,

how long will it take to reach a steady state concentration? (V d 35 liters and Cl 48 ml/min)

Since theophylline is used in the form of aminophylline, what would be the rate of infusion?

EXERCISE NO 22

Aspirin is an acidic drug with pKa of 3.5. What is the degree of ionization in the stomach

(pH 2.5), proximal duodenum (pH 4.5) and distal duodenum (pH 5.5)? If the pH of urine is

increased from 6 to 7.5, what will be the extent of ionization?

EXERCISE NO 23

A drug is given as 100 mg single dose resulting in a peak plasma concentration 20 mcg/ml.

Presuming a rapid distribution and negligible elimination prior to measuring the peak plasma

level, what is the volume of distribution?

EXERCISE NO 24

Pharmacokinetic Calculations and Exercises

A drug with a half life of 12 hours is administered by continuous IV infusion. How long will it

take for the drug to reach 90 percent of the final steady state concentration?

EXERCISE NO 25

An antibiotic with the Vd of 40L and Clr of 80ml/min is given by IV injection. Calculate the

maintenance dose to achieve a Css of 4mg/L if repeated every 6 hrs.

EXERCISE NO 26

Calculate the frequency of administration for a drug with a volume of

distribution of 500L and plasma t1/2 of 6hrs, to establish the CP ss of 4mg/L if

administered in the dose 400mg?

EXERCISE NO 27

A 55yrs old man with colon cancer has consented to participate in a clinical trial

involving a new anti-cancer drug formulation. The drug is to be administered as

a continuous intravenous infusion at the rate of 10mg/hr. Plasma

concentrations were serially measured in this patient and the results are shown

below. Assuming that the steady state plasma concentration is 4mg/lt,

determine the t, CL, Vd of the drug.

1 0.6

2 1.19

4 2

8 2.9

10 3.4

16 3.62

20 3.81

24 3.9

28 4

32 4

EXERCISE NO 28

Pharmacokinetic Calculations and Exercises

large number of phenobarbitone tablets about 8 hrs earlier. Measurement of

plasma drug concentration reveals a concentration of 50 mg/lt. Assuming the

Vd of phenobarbitone to be 40 L and the half-life to be 100hrs. How much of

phenobarbitone did the patient consume?

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