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PRACTICE PROBLEM
Q1. Determine the total body clearance for a drug in a 70-kg male
patient. The drug follows the kinetics of a onecompartment
model and has an elimination half-life of 3 hours with an apparent
volume of distribution of 100
mL/kg.

Solution
First determine the elimination rate constant (k ) and then

For a patient weighing 70 Kg have been calculated as

Q2. Consider a drug that is eliminated by first-order renal excretion and

hepatic metabolism. The drug follows a onecompartment model and is
given in a single intravenous or oral dose. Working with the model
presented in,assume that a single dose (100 mg) of this drug is given
orally. The drug is 90% systemically available. The total amount of
unchanged drug recovered in the urine is 60 mg, and the total amount of
metabolite recovered in the urine is 30 mg (expressed as milligram
equivalents to the parent drug). According to the literature, the
elimination half-life for this drug is 3.3 hours and its apparent volume of
distribution is 1000 mL. From the information given, find (a) the total
body clearance, (b) the renal clearance, and (c) the nonrenal clearance of
the drug.
Solution for the question A.

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b. Renal clearance. First find k e :

c. Non-renal clearance

alternatively

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Q3.An antibiotic is given by IV bolus injection at a dose of 500 mg. The

apparent volume of distribution was 21 L and the elimination half-life
was 6 hours. Urine was collected for 48 hours, and 400 mg of
unchanged drug was recovered. What is the fraction of the dose excreted
unchanged in the urine? Calculate a/ k b/ k e , c/ Cl T , d/ Cl R , and e/
Clh .
Solution
Since the elimination half-life, t 1/2 , for this drug is 6 hours, a urine
collection for 48 hours represents 8 x t 1/2 ,which allows for greater than
99% of the drug to be eliminated from the body. The fraction of drug
excreted unchanged in the urine, f e , and recalling that f = 1 for drugs
given by IV bolus injection.

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Alternatively

Q4.A new antibiotic is actively secreted by the kidney; V D is 35 L in

the normal adult. The clearance of this drug is 650 mL/min.
1. What is the usual t1/2 for this drug?
2.What would be the new t1/2 for this drug in an adult with partial renal
failure whose clearance of the antibiotic was only 75 mL/min?
First find the value of K which is =0.693/t1/2

Cl=kVd=>650ml/min=35000L*k
K=650ml/m /35000L=0.01857/min
Since k=0.693/t1/2 then t1/2 is 0.693/0.01857 min
=37.3 min

Q5. What would be the new t 1/2 for this drug in an adult with partial
renal failure whose clearance of the antibiotic was only 75 mL/min?

Solution for this one is

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Q6. A single 250-mg oral dose of an antibiotic is given to a young man

(age 32 years, creatinine clearance 122 mL/min, 78 kg). From the
literature, the drug is known to have an apparent V D equal to 21% of
body weight and an elimination half-life of 2 hours. The dose is
normally 90% bioavailable. Urinary excretion of the unchanged drug is
equal to 70% of the absorbed dose.
a. What is the total body clearance for this drug?
b. What is the renal clearance for this drug?
c. What is the probable mechanism for renal clearance of this drug?

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Q7. A drug with an elimination half-life of 1 hour was given to a male

patient (80 kg) by intravenous infusion at a rate of 300 mg/hr. At 7 hours
after infusion, the plasma drug concentration was 11micro gram/mL.
a. What is the total body clearance for this drug?
b. What is the apparent V D for this drug?
c. If the drug is not metabolized and is eliminated only by renal
excretion, what is the renal clearance of this drug?
d. What is the probable mechanism for renal clearance of this drug?

Q8. In order to rapidly estimate the renal clearance of a drug in a patient,

a 2-hour postdose urine sample was collected and found to contain 200
mg of drug. A midpoint plasma sample was taken (1 hr postdose) and
the drug concentration in plasma was found to be 2.5 mg%. Estimate the
renal clearance for this drug in the patient.

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Q9. According to the manufacturer, after the antibiotic cephradine

(Velosef), given by IV infusion at rate of 5.3mg/kg per hour to 9 adult
male volunteers (average weight, 71.7 kg), a steady-state serum
concentration of 17microgram/mL was measured. Calculate the average
total body clearance for this drug in adults.

Q10. What is the difference between drug clearance and creatinine

clearance?
Answer With most drugs, total body clearance (often termed
"clearance") is the sum of renal and nonrenal clearances. Creatinine is an
endogenous marker that accumulates in the blood when renal function is
impaired. Creatinine is excreted by glomerular filtration and is not
reabsorbed. Creatinine clearance is a measure of glomerular filtration
rate. Renal clearance is therefore proportional to creatinine clearance but
not equal to it, since most drugs are reabsorbed to some extent, and some
drugs are actively secreted.
9. Explain why plasma protein binding will prolong the renal clearance
of a drug that is excreted only by glomerular filtration but does not affect
the renal clearance of a drug excreted by both glomerular filtration and
active tubular secretion?

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Q11. A new antibiotic drug was given in a single

intravenous bolus of 4 mg/kg to five healthy male adults
ranging in age from 23 to 38 years (average weight 75
kg). The pharmacokinetics of the plasma drug
concentration–time curve for this drug fits a one-
compartment model. The equation of the curve that best
fits the data is Determine the following (assume units of
microgram/mL for C p and hr for t):
a. What is the t 1/2?
b. What is the V D?
c. What is the plasma level of the drug after 4 hours?
d. How much drug is left in the body after 4 hours?
e. Predict what body water compartment this drug might
occupy and explain why you made this
prediction.
f. Assuming the drug is no longer effective when levels
decline to less than 2 g/mL, when should you
administer the next dose?

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Q12. Morphine clearance, Cl T, for a 75-kg male patient is 1800 mL/min.

After an oral dose, 4% of the drug is excreted unchanged in the urine (f
e = 0.04). The fraction of drug absorbed after an oral dose of morphine
sulfate is 24% (F = 0.24). Hepatic blood flow is about 1500 mL/min.

Does morphine have any extrahepatic metabolism?

Answer
Solution
Since f e = 0.04, renal clearance Cl r = 0.04Cl T and nonrenal clearance Cl nr =
(1 – 0.04) Cl T = 0.96Cl T.Therefore, Cl nr = 0.96 x 1800 mL/min = 1728
mL/min. Since hepatic blood flow is about 1500 mL/min, the drug appears to be
metabolized faster than the rate of hepatic blood flow. Thus, at least some of the
drug must be metabolized outside the liver. The low fraction of drug absorbed after
an oral dose indicates that much of the drug is metabolized before reaching the
systemic circulation.

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Q13. A new broad-spectrum antibiotic was administered by rapid intravenous injection to a 50-
kg woman at a dose of 3 mg/kg. The apparent volume of distribution of this drug was equivalent
to 5% of body weight. The elimination half-life for this drug is 2 hours.
 a. If 90% of the unchanged drug was recovered in the urine, what is the renal
excretion rate constant?
 b. Which is more important for the elimination of the drugs, renal excretion or
biotransformation? Why?

b. Renal excretion, 90% of the drug is excreted unchanged.

Q14. A 50-kg woman was given a single IV dose of an antibacterial drug at a dose level of 6
mg/kg. Blood samples were taken at various time intervals. The concentration of the drug (C p)
t(hr) C p ( was determined in the plasma fraction of each blood sample and the
following data were obtained
µg/mL)
0.25 8.21
0.50 7.87
a. What are the values for V D, k, and t 1/2 for this drug?
1.00 7.23 b. This antibacterial agent is not effective at a plasma concentration of
3.00 5.15 less than 2 g/mL. What is the
duration of activity for this drug?
6.00 3.09 c. How long would it take for 99.9% of this drug to be eliminated?
d. If the dose of the antibiotic were doubled exactly, what would be the
12.0 1.11 increase in duration of activity?

18.0 0.40
Solution =Dose (IV bolus) = 6 mg/kg x 50 kg = 300 mg

(1) Plot the data on semilog

graph paper and use two points from the line of best fit.

T(hr) Cp(Microgram/ml)

2 6
6 3

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Alternatively, time t may be found from a graph of C p versus t

c. Time required for 99.9% of the drug to be eliminated:

d. If the dose is doubled, then C 0 p will also double. However, the elimination half-life or first-
order rate
constant will remain the same. Therefore,

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Notice that doubling the dose does not double the duration of activity.

Q15. An antibiotic has a volume of distribution of 10 L and a k of 0.2 hr– 1. A steady-

state plasma concentration of 10 g/mL is desired. The infusion rate needed to maintain this
concentration can be determined as follows.

Q16.A patient was given an antibiotic (t 1/2 = 6 hr) by constant IV infusion at a

rate of 2 mg/hr. At the end of 2 days, the serum drug concentration was 10 mg/L.
Calculate the total body clearance Cl T for this antibiotic.The total body clearance
may be estimated from Equation 5.7. The serum sample was taken after 2 days or
48 hours of infusion, which time represents 8 x t 1/2, therefore, this serum drug
concentration approximates the C SS

Q17.An antibiotic has an elimination half-life of 3–6 hours in the general population. A patient
was given an IV infusion of an antibiotic at an infusion rate of 15 mg/hr. Blood samples were
taken at 8 and at 24 hours and plasma drug concentrations were 5.5 and 6.5 mg/L, respectively.
Estimate the elimination half-life of the drug in this patient.
Solution
Because the second plasma sample was taken at 24 hours, or 24/6 = 4 half-lives after infusion,
the plasma drug concentration in this sample is approaching 95% of the true plasma steady-

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state drug concentration assuming the extreme case of t 1/2 = 6 hours.

Q18. A physician wants to administer an anesthetic agent at a rate of 2 mg/hr by IV infusion.

The elimination rate constant is 0.1 hr– 1, and the volume of distribution (one compartment) is
10 L. What loading dose should be recommended if the doctor wants the drug level to reach 2
mcg/mL immediately?
Solution

To reach C SS instantly,

Q19. What is the concentration of a drug 6 hours after administration of a loading dose of 10 mg
and simultaneous infusion at 2 mg/hr (the drug has a t 1/2 of 3 hr and a volume of distribution of
10 L)?
Solution

4. A patient was infused for 6 hours with a drug (k = 0.01 hr– 1; V D = 10 L) at a rate of 2
mg/hr. What is the concentration of the drug in the body 2 hours after cessation of the infusion?

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Solution

Alternatively, when infusion stops, C'p is calculated:

Q20. An antibiotic is to be given to an adult male patient (58 years old, 75 kg) by IV infusion.
The elimination half-life is 8 hours and the apparent volume of distribution is 1.5 L/kg. The drug
is supplied in 60-mL ampoules at a drug concentration of 15 mg/mL. The desired steady-state
drug concentration is 20 g/mL.
a. What infusion rate, in milliliters per hour, would you recommend for this patient?
b. What loading dose would you recommend for this patient? By what route of administration
would you give the loading dose? When?
c. Why should a loading dose be recommended?
d. According to the manufacturer, the recommended starting infusion rate is 15 mL/hr. Do you
agree with this recommended infusion rate for your patient? Give a reason for your answer.
e. If you were to monitor the patient's serum drug concentration, when would you request a
blood sample? Give a reason for your answer.
f. The observed serum drug concentration is higher than anticipated. Give two possible reasons
based on sound pharmacokinetic principles that would account for this observation.

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Q21. A single IV bolus injection containing 500 mg of cefamandole nafate (Mandol, Lilly) is given
to an adult female patient (63 years, 55 kg) for a septicemic infection. The apparent volume of
distribution is 0.1 L/kg and the elimination half-life is 0.75 hour. Assuming the drug is eliminated
by first-order kinetics and may be described by a one-compartment model, calculate the
following:
a. The C p 0
b. The amount of drug in the body 4 hours after the dose is given
c. The time for the drug to decline to 0.5 g/mL, the minimum inhibitory concentration for
streptococci

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Q22.The maintenance dose of gentamicin is 80 mg every 6 hours for a patient with normal renal
function.Calculate the maintenance dose for a uremic patient with creatinine clearance of 20
mL/min. Assume a normal creatinine clearance of 100 mL/min.
Solution
From the literature, gentamicin is reported to be 100% excreted by the kidney (ie, fe = 1). Using
Equation

The maintenance dose is 16 mg every 6 hours. Alternatively, the dosing interval can be adjusted
without changing the dose:

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Q23.A drug has an elimination half-life of 2 hours and a volume of distribution of 40 L. The drug
is given at a dose of 200 mg every 4 hours by multiple IV bolus injections. Predict the plasma
drug concentration at 1 hour after the third dose.

Alternatively, one may conclude that for a drug whose elimination t 1/2 is 2 hours, the predicted
plasma drug concentration is approximately at steady state after 3 doses or 12 hours. Therefore,
the above calculation may be simplified to the following:

Q24.The elimination half-life of an antibiotic is 3 hours and the apparent volume of distribution is
20% of body weight. The therapeutic window for this drug is from 2 to 10 g/mL. Adverse toxicity
is often observed at drug concentrations above 15 g/mL. The drug will be given by multiple IV
bolus injections.

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a. Calculate the dose for an adult male patient (68 years old, 82 kg) with normal renal function
to be given
every 8 hours.
b. Calculate the anticipated C ∠max and C ∠min values.
c. Calculate the C ∠av value.
d. Comment on the adequacy of your dosage regimen.

d. In the above dosage regimen, the C ∠min of 1.59 mg/L is below the desired C ∠min of 2 mg/L.
Alternatively, the dosage interval, , could be changed to 6 hours.

Q25.Tetracycline hydrochloride (Achromycin V, Lederle) is prescribed for a young adult male

patient (28 years old, 78 kg) suffering from gonorrhea. According to the literature, tetracycline
HCl is 77% orally absorbed, is 65% bound to plasma proteins, has an apparent volume of
distribution of 0.5 L/kg, has an elimination half-life of 10.6 hr, and is 58% excreted unchanged in
the urine. The minimum inhibitory drug concentration (MIC) for gonorrhea is 25–30 g/mL.
a. Calculate an exact maintenance dose for this patient to be given every 6 hours around the
clock.
b. Achromycin V is available in 250-mg and 500-mg capsules. How many capsules (state dose)
should the patient take every 6 hours?

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c. What loading dose using the above capsules would you recommend for this patient?

Q26.Cefotaxime has a volume of distribution of 0.17 L/kg and an elimination half-life of 1.5 hr.
What is the peak plasma drug concentration in a patient weighing 75 kg after receiving 1 g IV of
the drug 3 times daily for 3 days? Try to exceed your vision!!

Q27.Gentamicin has an average elimination half-life of approximately 2 hours and an apparent

volume of distribution of 20% of body weight. It is necessary to give gentamicin, 1 mg/kg every
8 hours by multiple IV injections, to a 50-kg woman with normal renal function. Calculate (a) C
max, (b) C min, and (c) C ∠av
(Try to exceed your vision!!)

Q28.Explain why plasma protein binding will prolong the renal clearance of a drug that is
excreted only by glomerular filtration but does not affect the renal clearance of a drug excreted
by both glomerular filtration and active tubular secretion.
Answer:Protein-bound drugs behave as large molecules that mw >500 and do not get filtered at
the glomerulus
 Glomerular filtration of drugs is directly related to the free or nonprotein-bound drug
concentration in the plasma.
 As the free drug concentration in the plasma increases, the glomerular filtration for the
drug increases proportionately
 thus increasing renal drug clearance for some drugs
 drug protein binding has very little effect on the elimination half-life of the drug excreted
mostly by active tubular secretion.
 Because drug protein binding is reversible, drug bound to plasma protein rapidly
dissociates as free drug is secreted by the kidneys

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Q29.At a high concentrations of the drug in the plasma, the percentage of drug excreted by
active secretion decreases. Why?
Q30. At low concentrations of the drug in the plasma, the percentage of drug excreted by active
secretion increases. Why?

Q31.The total body clearance of a drug is 10 mL/min/kg. The renal clearance is not known. From
a urinary drug excretion study, 60% of the drug is recovered intact and 40% is recovered as
metabolites. What is the hepatic clearance for the drug, assuming that metabolism occurs in the
liver?
Solution

where f e = percent of intact drug recovered in the urine.

32/ Phenytoin was administered to a patient at dosing rates of 150 and 300 mg/day,
respectively. The steadystate plasma drug concentrations were 8.6 and 25.1 mg/L, respectively.
Find the K M and V max of this patient.
What dose is needed to achieve a steady-state concentration of 11.3 mg/L?
Solution
There are three methods for solving this problem, all based on the same basic equation (Eq.
9.11).

Combine the two Equestion

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Thank you for your interest of exceeding your vision in near the future!!!! By SG

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