Dr.

Nutan, 2009
Drug distribution and protein binding
1. Which of the following can be considered true for apparent volume of distribution?
a)
b)
c)
d)
e)

It is the combined volume of blood, tissue and other organs where drug is distributed.
It is a true physiological volume.
It is high for a drug, which is mostly concentrated in blood.
It gives us idea about the distribution of a drug in the body.
It can be calculated only when drug concentrations in blood and tissue are the same.

Explanation:
Apparent volume of distribution, VD is not a true volume. Therefore, combining the actual
volumes of blood, tissue, and other organs does not give the apparent volume of distribution.
Volume of distribution is an indicator of drug distribution throughout the body. Drugs with high
VD are more distributed to the peripheral tissues and drugs with low VD are mostly present in
blood. Drug concentrations in blood and tissue do not have to be the same to calculate VD.
2. What type of bond is NOT commonly found in protein binding of drugs?
a)
b)
c)
d)
e)

Electrostatic
Hydrogen
Covalent
van der Waals
Hydrophobic

Explanation:
Protein binding is generally reversible. Therefore, drugs bind with plasma proteins and come off.
Covalent bond is very rare. It is very strong and may make irreversible complex of drug with
plasma proteins. An example is the binding of cisplatin with serum albumin.
3. 1-Acid glycoprotein is the most abundant plasma protein in human.
a) True
b) False
Explanation:
Albumin is the most abundant protein in plasma.
4. Calculate the percent protein bound of a drug in tissues, if plasma protein binding and
volume of distribution of the drug are 20% and 55 L, respectively. The volumes of plasma
and tissue are 3 L and 39 L, respectively.
a)
b)
c)
d)
e)

15%
40%
20%
60%
85%

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Dr. Nutan, 2009

Explanation:
f up
VD = VB +
VT
f ut
0 .8
55 L = 3 L +
39 L
f ut
f ut = 0.6
Therefore, 60% drug is unbound in tissue. It means, 100 60 = 40% drug is protein bound in
tissues.
5. Hepatic clearance of a drug is 15 L/hr. Calculate its hepatic extraction ratio considering a
blood flow of 1500 ml/min.
a)
b)
c)
d)
e)

0.01
0.50
0.99
0.17
0.83

Explanation:
Cl H = Q E
Q = 1500 ml/min = 90 L/hr
Cl
15 L / hr
E= H =
= 0.17
Q
90 L / hr
6. Calculate the concentration of drug with a hepatic extraction ratio of 0.15 in blood entering
liver when the concentration in blood leaving the liver is 182 mg/L.
a)
b)
c)
d)
e)

158 mg/L
182 mg/L
209 mg/L
155 mg/L
214 mg/L

Explanation:
C C out
E = in
Cin
C 182 mg / L
0.15 = in
C in
C in = 214 mg / L

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7. Which of the following statements is NOT true for procainamide, a drug with high clearance
and large volume of distribution?
a)
b)
c)
d)
e)

Apparent volume of distribution increases as protein binding decreases.

Total clearance does not change with protein binding.
Half life of the drug remains the same as protein binding decreases.
Concentration of free drug in plasma increases as protein binding decreases.
Total concentration of drug in plasma does not change with protein binding.

Explanation:
The following things happen due to change in protein binding of a drug with high clearance and
large volume of distribution. When protein binding decreases, more drugs become free and
therefore, the concentration of free drug increases. Apparent volume of distribution increases
almost proportionally as free fraction of drug increases (as protein binding decreases), total
clearance remains unchanged. Since the total drug concentration in blood is related to the total
clearance, the total concentration in blood does not change. Since VD increases as protein
binding increases, half life also increases.

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Renal elimination
1. Which of the following is NOT true for drug excretion?
a)
b)
c)
d)
e)

Drug excretion refers to the elimination of intact drugs.

Some drugs are almost completely eliminated by excretion.
Volatile drugs are generally excreted by lungs.
Rate of excretion may be affected by renal dysfunction.
Drugs are excreted only by kidneys.

Explanation:
Kidneys are the major organs for drug excretion. However, drugs can also be excreted
(eliminated intact) by other organs/means, e.g., lungs, saliva, milk, sweat, etc.
2. Drugs can be excreted through all of the following body products EXCEPT this one.
a)
b)
c)
d)
e)

Urine
Bile
Milk
Sweat
Enzyme

Explanation:
Urine, milk, and sweat are excreted outside the body and some drugs can be excreted through
them. Bile is released in the GI tract and from there it can be excreted through feces. Therefore,
some drugs can be excreted out of the body through bile as well. Enzymes, however, do not carry
any drugs.
3. What is the total renal clearance of a drug if its glomerular filtration, tubular secretion, and
tubular reabsorption are 120, 50, and 80 ml/min, respectively?
a)
b)
c)
d)
e)

10 ml/min
50 ml/min
90 ml/min
150 ml/min
250 ml/min

Explanation:
Total renal clearance = Glomerular filtration + Active tubular secretion Tubular reabsorption =
120 + 50 80 = 90 ml/min

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4. If the glomerular filtration of a drug is 96 ml/min, what portion of the drug is bound to
plasma protein assuming GFR to be 120 ml/min?
a)
b)
c)
d)
e)

0%
24%
96%
20%
100%

Explanation:
Cl R ( f ) = f u .GFR
96 ml / min
= 0 .8
GFR 120 ml / min
Therefore, 80% drug is free in plasma. It means, 20% drug is protein bound.
fu =

Cl R ( f )

5. Which of the following statements is true for tubular secretion of drug in kidneys?
a)
b)
c)
d)
e)

Tubular secretion is a passive transport process.

Both acidic and basic drugs are secreted by the same carrier system.
Protein binding can greatly affect tubular secretion.
Tubular secretion occurs in the distal tubule.
An increase in tubular secretion increases total renal clearance.

Explanation:
An increase in tubular secretion increases total renal excretion and thereby the total renal
clearance because clearance due to secretion adds up to the clearance due to glomerular
filtration. Tubular secretion is an active transport process. Weakly acidic and weakly basic drugs
have two separate carrier systems. Protein binding has very little effect on tubular secretion.
Tubular secretion occurs at the proximal convoluted tubule.
6. A drug, which does not bind to plasma protein, has a total renal clearance of 100 ml/min.
Which of the following mechanism(s) is/are CERTAINLY involved in the renal excretion of
this drug? Consider GFR to be 120 ml/min.
a)
b)
c)
d)
e)

Glomerular filtration only

Glomerular filtration and active tubular secretion
Glomerular filtration and tubular reabsorption
Glomerular filtration, active tubular secretion and tubular reabsorption
Active tubular secretion and tubular reabsorption

Explanation:
Cl R ( f ) = f u .GFR = 1 120 ml/min = 120 ml / min
Since total renal clearance (100 ml/min) is smaller than the clearance by filtration (120 ml/min),
there must be some reabsorption mechanism involved in the process.

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7. Estimate creatinine clearance in a 50-year old, 121-pound and 52 tall female patient whose
serum creatinine level is 1 mg%.
a)
b)
c)
d)
e)

58.44 ml/min
53.23 ml/min
68.75 ml/min
62.62 ml/min
128.56 ml/min

Explanation:
IBW ( kg ) = 45.5 + 2.3 height in inches over 5 ft ( for females ) = 45.5 + 2.3 2 = 50.1 kg
Actual body weight 121 2.2
=
= 1.1 = 110%
IBW
50.1
Since the actual body weight is only 110% times the IBW, actual body weight should be used to
calculate creatinine clearance.
[140 age ( year )] body weight (kg ) 0.85 ( for females )
Cl Cr ( ml / min) =
72 C Cr (mg % )
[140 50] 55 0.85 = 58.44 ml/min
Cl Cr (ml / min) =
72 1
8. Atenolol has a renal clearance of 140 ml/min in subjects with normal kidney function (ClCr of
120 ml/min). Estimate the renal clearance of the drug in a patient with ClCr of 90 ml/min.
a)
b)
c)
d)
e)

110 ml/min
187 ml/min
77 ml/min
170 ml/min
105 ml/min

Explanation:
Cl Cr ( d ) Cl R ( d )
=
Cl Cr ( n ) Cl R ( n )
Cl R ( d )
90 ml/min
=
120 ml/min 140 ml/min
Cl R ( d ) = 105 ml/min

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Dr. Nutan, 2009

Pharmacokinetics of single oral dose
1. Which of the following is a true statement for oral administration of a single dose of a drug?
f)
g)
h)
i)
j)

No absorption occurs once Cmax is obtained.

Generally the last phase in the curve represents elimination.
The rate of elimination is generally higher than the rate of absorption before Cmax.
The rate of absorption is the highest at Cmax.
Elimination starts only when Cmax is reached.

Explanation:
Drug absorption is generally a first order process. Therefore, absorption virtually never ends.
However, absorption becomes negligible at the very end of the process. Therefore, last few data
points can be considered to be devoid of absorption and it is from elimination only. Absorption
rate is the highest immediately after drug administration since the rate is proportional to the
amount of drug present and the highest amount of drug is present in the GIT at that time. Over
the time, since the amount of drug in the GIT decreases, rate of absorption slows down.
Therefore, upon administration the absorption rate decreases all the time. Elimination rate, on the
other hand is zero at time zero. As soon as some amount of drug appears in blood, elimination
starts. Since at the beginning the absorption rate is too high, it is higher than the elimination rate
and plasma concentration goes up. However, as mentioned above, absorption rate slows down
and at one point it becomes equal to the elimination rate. This is the Cmax. Beyond Cmax
absorption rate becomes smaller than elimination rate and hence, plasma concentration goes
down. Eventually the absorption rate slows down so much that at the end of the plasma
concentration over time curve it can be considered to be zero.
2. Which of the following is a true statement for oral administration of a single dose of a drug?
a)
b)
c)
d)
e)

At Cmax, the rate of absorption is higher than the rate of elimination.

The rate of absorption is generally constant throughout the process.
At Cmax, the rate of elimination is higher than the rate of absorption.
At Cmax, the rate of elimination is zero.
Absorption can be found in postabsorption phase.

Explanation:
Drug absorption is generally a first order process. Therefore, absorption virtually never ends.
Hence, absorption occurs in the postabsorption phase (after Cmax), too. However, absorption
becomes negligible at the very end of the process. Therefore, last few data points can be
considered to be devoid of absorption and it is from elimination only. Absorption rate is the
highest immediately after drug administration since the rate is proportional to the amount of drug
present and the highest amount of drug is present in the GIT at that time. Over the time, since the
amount of drug in the GIT decreases, rate of absorption slows down. Therefore, upon
administration the absorption rate decreases all the time. Elimination rate, on the other hand is
zero at time zero. As soon as some amount of drug appears in blood, elimination starts. Since at
the beginning the absorption rate is too high, it is higher than the elimination rate and plasma
concentration goes up. However, as mentioned above, absorption rate slows down and at one
point it becomes equal to the elimination rate. This is the Cmax. Beyond Cmax absorption rate
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Dr. Nutan, 2009

becomes smaller than elimination rate and hence, plasma concentration goes down. Eventually
the absorption rate slows down so much that at the end of the plasma concentration over time
curve it can be considered to be zero.
3. Calculate the time to reach the maximum concentration after the administration of a single
oral dose of a drug whose half life of elimination is 2.31 hr. The absorption rate constant for
the drug is 1.5 hr1.
a)
b)
c)
d)
e)

0.53 hr
0.58 hr
1.34 hr
2.31 hr
0.89 hr

Explanation:
Be careful about two things. You are looking for the tmax, not the Cmax. Also, you know the value
of t, not K.
0.693
0.693
K=
=
= 0.3 hr 1
t1 2
2.31 hr
1

t max

1.5 hr
K
ln
ln a
0.3 hr 1
K
=
=
= 1.34 hr
K a K 1.5 hr 1 0.3 hr 1

4. What is the elimination rate constant of a drug that shows the following data after the
administration of 10 mg of dose by oral route?
Time (hr)
Cp (g/ml)
0.5
5.32
1
6.88
2
7.93
4
7.71
6
6.50
8
5.32
12
3.33
16
2.50
24
1.42
a)
b)
c)
d)
e)

0.0710 hr1
0.0430 hr1
0.1557 hr1
0.1059 hr1
1.9286 hr1

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Explanation:
First of all, you do not need to use the dose for this calculation. This is a data from
administration of a single dose by oral route. The process starts with absorption, immediately
followed by elimination. Absorption rate slows down at the end so much that it can be
disregarded and the last segment of the curve virtually represents elimination only. Last three
points should be used in natural log forms using regression equations in calculator to find out
the slope. The negative value of the slope would be the elimination rate constant. Here I will
show you the process using two points.
3.33 g / ml
ln
Y Y1
ln 3.33 g / ml ln 1.42 g / ml
1.42 g / ml
Slope = 2
=
=
= 0.071 hr 1
X 2 X1
12 hr 24 hr
12 hr
Therefore, K = 0.071 hr1.
5. Calculate the time to reach the maximum concentration using the appropriate equation if the
absorption rate constant in the previous question is 3.017 hr1.
a)
b)
c)
d)
e)

7.93 hr
3.02 hr
1.27 hr
2.50 hr
9.76 hr

Explanation:
K in the previous question was 0.071 hr1.
3.017 hr 1
Ka
ln
ln
0.07 hr 1
K =
t max =
= 1.28 hr
K a K 3.017 hr 1 0.07 hr 1
6. Calculate area under the plasma concentration versus time curve of the following profile
obtained after the administration of 100 mg of a single dose by oral route?
Time (hr)
Cp (g/ml)
0
0.00
0.5
5.32
1
6.88
2
7.93
4
7.71
6
6.50
8
5.32
12
3.33
16
2.50
24
1.42

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Dr. Nutan, 2009

a)
b)
c)
d)
e)

118 g-hr/ml
24 g-hr/ml
81 g-hr/ml
29 g-hr/ml
98 g-hr/ml

Explanation:
The dose is not required here. AUC can be calculated using the following equation.
(C + C 2 ) (t 2 t1 )
AUC = 1
2
Therefore, AUC from time 0 to 0.5 hr would be as follows.
(0 + 5.32 ) (0.5 0 ) = 1.33 g.hr / ml
AUC 0 0.5 =
2
Similarly, the other AUCs can be calculated as follows.
AUC0.51 = 3.05 g.hr / ml

AUC12 = 7.405 g.hr / ml

AUC24 = 15.64 g.hr / ml
AUC 46 = 14.21 g .hr / ml
AUC 68 = 11.82 g .hr / ml
AUC812 = 17.3 g.hr / ml
AUC1216 = 11.66 g .hr / ml
AUC1624 = 15.68 g.hr / ml
AUC of the last part of the profile (time 24 hr to infinity) can be calculated using the following
equation.
C
AUC Last = Last
K
Calculate K as usual using only the last 3 data points on log scale.
3.33 g / ml
ln
Y Y1
ln 3.33 g / ml ln 1.42 g / ml
1.42 g / ml
Slope = 2
=
=
= 0.07 hr 1
X 2 X1
12 hr 24 hr
12 hr
Therefore, K = 0.071 hr1.
C
1.42 g / ml
AUC Last = AUC 24 = Last =
= 20.29 g .hr / ml
K
0.07 hr 1
Therefore, AUCTotal = 118 g.hr / ml

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7. Estimation of which of the following parameters from oral administration of a single dose
requires the IV data along with the oral data?
a)
b)
c)
d)
e)

Elimination rate constant (K)

Bioavailability (F)
Area under the curve (AUCOral)
Time to reach maximum concentration (tmax)
Absorption rate constant (Ka)

Explanation:
Bioavailability of a drug after oral administration is basically the ratio of AUCOral to AUCIV,
when the same doses are given by both routes. Therefore, IV data is required to calculate
bioavailability of a drug by oral route. All the other parameters for oral administration can be
calculated without the help of the IV data. Elimination rate constant can be determined from the
slope of the straight line of the last three data point on log scale. AUCOral can be calculated from
the individual area under two adjacent data points using trapezoidal rule. The last segment of
AUC can be calculated with the help of K and calculating K does not require IV data as shown
earlier. tmax can be calculated from the equation that involves K and Ka, both of which can be
obtained from oral data only. Ka can be determined from the slope of the residual line that is
obtained from the difference of the extrapolated line and the first part of the oral data.
8. If the plasma profile obtained after the administration of a 100 mg of a single oral dose of a
drug yields an area under the curve of 118 g-hr/ml, calculate the oral bioavailability. If 50
mg of the same drug is given by an intravenous bolus injection, an area under the curve of 92
g-hr/ml is obtained.
a)
b)
c)
d)
e)

50%
53%
64%
32%
36%

Explanation:
AUC Oral DoseOral 118 100
=
= 0.64 = 64%
F=
92 50
AUC IV Dose IV
9. Which of the following data indicates a flip-flop phenomenon?
a)
b)
c)
d)
e)

K = 0.02 hr1 and Ka = 0.1 hr1

K = 0.3 hr1 and Ka = 1.3 hr1
K = 0.5 min1 and Ka = 0.08 min1
K = 0.007 min1 and Ka = 0.05 min1
K = 0.075 day1 and Ka = 1.19 day1

Explanation:
In most cases absorption rate constant (Ka) is much higher than elimination rate constant (K).
The last segment of the oral data represents only elimination and the slope of this part can be
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Dr. Nutan, 2009

used to determine K. In some cases, however, absorption of the drug is too slow by nature, or it
is made slow intentionally to prepare an extended release product. In these cases, K becomes
higher than Ka and the last segment of the oral data represents only absorption and Ka can be
found from its slope. These rare cases are called flip-flop phenomenon. In all of the answer
choices except one, Ka is higher than K and therefore, they are not flip-flop phenomenon.

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Pharmacokinetics of multiple oral dose
1. Plasma concentrations of a drug after administration of multiple oral doses are determined by
which of the following?
a)
b)
c)
d)
e)

Principle of residual
Principle of accumulation
Principle of superposition
Method of feathering
Method of steady state

Explanation:
It is true that drug accumulates in blood after multiple dosing. However, it is known as the
principle of superposition.
2. What happen when the dose of an oral multiple dose therapy is increased?
a) Cmax increases proportionally but Cmin remains unchanged.
b) Fluctuation between Cmax and Cmin increases proportionally.
c) Cave increases proportionally but fluctuation between Cmax and Cmin remains
unchanged.
d) Cave remains unchanged but the fluctuation between Cmax and Cmin increases
proportionally.
e) Cave increases but it is not proportional to the increase in dose.
Explanation:
If the dose of an oral multiple therapy is increased keeping the interval the same, Cmax, Cmin,
Cave, and the fluctuation between Cmax and Cmin increase proportionally.
3. What happens if the dosing of a multiple oral dose treatment is changed from 400 mg every 8
hr to 200 mg every 4 hr?
a)
b)
c)
d)
e)

The maximum concentration at steady state remains the same.

The average steady state concentration remains the same.
Both maximum and minimum concentration at steady state decrease.
The fluctuation in plasma level at steady state increases.
The minimum concentration at steady state remains the same.

Explanation:
If the dosing rate (dose per unit time) is kept the same, Cave remains unchanged. However, since
the dose is decreased, Cave, Cmax, and Cmin will change. Since smaller doses are given in
shorter duration, fluctuation will decrease to half (Dose is decreased to half.). Cmax goes down
and Cmin will increase to maintain the same Cave. These can be seen easily from the following
figure.

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4. How much time will be required to reach 90% of the steady state if 500 mg of doses are
given every 6 hours? The clearance and volume of distribution for this drug are 0.48 L/hr and
50 L, respectively.
a)
b)
c)
d)
e)

20 days
72 hours
20 hours
40 hours
10 days

Explanation:
Cl = K V D
Cl 0.48 L / hr
K=
=
= 0.0096 hr 1
VD
50 L
0.693
0.693
t1 2 =
=
= 72 hr
K
0.0096 hr 1

t 90
% = 3.3 t1 2 = 3.3 72 hr = 238 hr 10 days

5. What average concentration in plasma at steady state do you expect from the administration
of 500 mg of oral doses every 4 hours in a patient with a body weight of 75 kg? The
clearance of the drug is 0.8 L/kg/hr and the fraction absorbed is 0.65.
a)
b)
c)
d)
e)

8.33 mg/L
1.67 mg/L
2.08 mg/L
5.34 mg/L
1.35 mg/L

Explanation:
Cl = 0.8 L / kg / hr 75 kg = 60 L / hr
FD0
0.65 500 mg

C ave
=
=
= 1.35 mg / L
Cl
60 L / hr 4 hr
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6. A drug has 80% bioavailability. Its volume of distribution, elimination rate constant, and
absorption rate constant are 20 L, 0.3 hr1, and 3.471 hr, respectively. Calculate the
minimum plasma concentration at steady state if 800 mg doses are administered orally every
6 hr.
a)
b)
c)
d)
e)

6.92 mg/L
17.78 mg/L
30.93 mg/L
25.40 mg/L
32.00 mg/L

Explanation:
FD0
Ka
e K

C min =

VD
K a K 1 e K
1

min

0.8 800 mg
3.47 hr 1
e 0.3 hr 6 hr
=

= 6.92 mg / L
1
20 L
3.47 hr 1 0.3 hr 1 1 e 0.3 hr 6 hr

7. What dose is needed to be given every 6 hr to obtain an average steady state concentration of
5 mg/L if the clearance of the drug is 20 ml/hr? The value of F is 1.
a)
b)
c)
d)
e)

600 g
100 g
2.4 mg
0.4 mg
200 g

Explanation:
Cl = 20 ml / hr = 0.02 L / hr
FD0
0.65 500 mg

C ave
=
=
= 1.35 mg / L
Cl
60 L / hr 4 hr
D0 =

C ave
Cl 5 mg / L 0.02 L / hr 6 hr
=
= 0.6 mg = 600 g
1
F

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Dr. Nutan, 2009

Clearance concepts
1. The fraction of dose excreted unchanged in urine is a measure of the contribution of renal
clearance to the total clearance.
a) True
b) False
Explanation:
Cl
fe = R
Cl
Therefore, the fraction excreted unchanged in urine is basically the ratio of renal clearance to the
total clearance. If fe goes up, the contribution of renal clearance to the total clearance increases.
For example, if fe is 0.2, 20% of the total clearance is due to the renal clearance. If fe increases to
0.6, 60% of the total clearance is due to the renal clearance.
2. The total body clearance of a drug is 250 ml/min. What is the hepatic clearance of this drug if
30% of a given dose is excreted unchanged in urine?
a)
b)
c)
d)
e)

425 ml/min
75 ml/min
250 ml/min
175 ml/min
120 ml/min

Explanation:
Cl R = f e Cl = 0.3 250 = 75 ml/min

Cl H = Cl Cl R = 250 75 = 175 ml/min

3. The nonrenal clearance of a drug is 236 ml/min. Calculate the renal clearance if the fraction
excreted unchanged in urine is 0.2.
a)
b)
c)
d)
e)

59 ml/min
354 ml/min
120 ml/min
590 ml/min
295 ml/min

Explanation:
f NR = 1 f e = 1 0.2 = 0.8
Cl
f NR = NR
Cl
Cl
236 ml/min
Cl = NR =
= 295 ml / min
f NR
0 .8
Cl R = Cl Cl NR = 295 236 = 59 ml/min
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4. The overall clearance of a drug in a healthy person weighing 75 kg is 5 ml/kg/min. The
fraction of drug excreted unchanged in urine is 0.8. Recently because of a disease, kidneys of
this patient became only partially functional. If the fraction of drug excreted unchanged in
urine becomes 0.5 in diseased state, what would be the overall clearance of this drug when
the person is ill?
a)
b)
c)
d)
e)

300 ml/min
375 ml/min
600 ml/min
75 ml/min
150 ml/min

Explanation:
For the healthy personCl = 5 ml / kg / min 75 kg = 375 ml / min
Cl R = f e Cl = 0.8 375 = 300 ml/min
Cl NR = Cl Cl R = 375 300 = 75 ml/min
For the diseased personNonrenal clearance remains unchanged.
Cl NR = 75 ml / min
Be careful about one thing! Do not calculate renal clearance based on the total clearance of 375
ml/min using 0.5 375 ml/min = 187.5 ml/min and then add renal clearance with nonrenal
clearance to find total clearance as 187.5 + 75 = 262.5 ml/min. This is wrong! Remember, the
total clearance for this diseased person will be different because of decreased renal function and
therefore, renal clearance cannot be calculated using the total clearance of the healthy person.
Renal clearance will change.
f e + f NR = 1
f NR = 1 f e = 1 0.5 = 0.5
Cl
f NR = NR
Cl
Cl
75 ml / min
Cl = NR =
= 150 ml / min
f NR
0 .5
5. A 180 mg dose every 12 hours produces 15 mg/L plasma concentration in a healthy
individual. The bioavailability of the drug is 80%. Renal clearance constitutes 50% of the
total clearance. What would be the plasma concentration of the drug in an anephric (no renal
function) patient if the same dose is administered?
a)
b)
c)
d)
e)

15 mg/L
11 mg/L
22 mg/L
30 mg/L
7.5 mg/L
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Dr. Nutan, 2009

Explanation:
F ( D0 / )

=
Cave
Cl
F ( D0 / )
0.8 180 mg
=
= 0.8 L / hr
Cl =

15 mg / L 12 hr
C ave
f e = 0.5
Cl R = f e Cl = 0.5 0.8 = 0.4 L / hr
Cl NR = Cl Cl R = 0.8 0.4 = 0.4 L / hr
If there is no renal function, ClR(disease) is zero. In such case, Cl(d) = ClNR(d) = 0.4 L/hr.
FD0
shows us that if the dosing internal (D0/) is kept the same, the average
Cl
drug concentration at steady state is inversely proportional to the total clearance. Therefore, the
plasma concentration at diseased state can be obtained from the following equation.

Cl (d ) C ave (n )
=
Cl (n ) C ave
(d )

Equation C ave
=

0.8 L / hr
= 30 mg / L
Cl (d )
0.4 L / hr
One interesting thing in this problem is that it can be solved without knowing the total
clearances. The same answer would be obtained even with different total clearances. For
example, if the total clearance for the normal (healthy) individual were 10 L/hr, the total
clearance for the diseased person would have been 5 L/hr and the average drug concentration at
steady state would have been 30 mg/L, the same found with the different total clearances. This is
because if the clearance is reduced to half, plasma concentration would be doubled, as simple as
this.

C ave
( d ) = C ave ( n )

Cl (n )

= 15 mg / L

6. Cimetidine has a total clearance of 525 ml/min in healthy adults. Due to renal impairment,
the total clearance is reduced to 197 ml/min. If the original dosage regimen was scheduled as
800 mg twice daily, which of the following could be the adjusted dose in this patient?
a)
b)
c)
d)
e)

400 mg twice daily

800 mg daily
200 mg twice daily
200 mg three times daily
400 mg three times daily

Explanation:
Cl (d ) 800 mg 197 ml / min
Dose
Dose
=

= 25 mg / hr

=
12 hr
525 ml / min
(d ) (n ) Cl (n )
Therefore, the dosing rate has to be 25 mg per hour or 600 mg per day. This can be accomplished
with only 200 mg three times daily dosage regimen.

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Dr. Nutan, 2009

7. Determine the loading dose of a multiple dose treatment of a drug whose volume of
distribution and half life are 32 L and 36 hours, respectively. The regular doses are given
every 6 hours. The drug is only 20% absorbed and the desired average plasma concentration
at steady state is 10 mg/L.
a)
b)
c)
d)
e)

540 mg
185 mg
1088 mg
1694 mg
390 mg

Explanation:
Loading dose can be calculated using the following equation.
DM
DL = DM R =
1 e k
All the parameters except DM are known. DM should be calculated from the following equation.

C ave
KV D
DM =
F

K=

0.693 0.693
=
= 0.01925 hr 1
t1 2
36

C ave
KV D 10 mg / L 0.01925 hr 1 32 L 6 hr
=
= 184.8 mg
F
0.2
DM
184.8 mg
Therefore, DL = =
=
= 1694 mg
1
k
1 e
1 e 0.01925 hr 6 hr

DM =

Page 19 of 19