# Basic Pharmacokinetics REV. 00.1.

27 4-1
CHAPTER 4 I.V. Bolus Dosing
Author: Michael Makoid and John Cobby
Reviewer: Phillip Vuchetich
OBJECTIVES
For an IV one compartment model plasma and urine:
1. Given patient drug and/or metabolite concentration, amount, and/or rate vs. time
profiles, the student will calculate (III) the relevant pharmacokinetic parameters
available from IV plasma, urine or other excreta data: e.g.
2. The student will provide professional communication regarding the pharmacoki-
netic parameters obtained to patients and other health professionals.
3. The student will be able to utilize computer programs for simulations and data
analysis.
V
d
K k
m
k
r
AUC AUMC CL MRT t
1 2 ⁄
, , , , , , , ,
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-2
4.1 I.V. Bolus dosing of Parent compound
4.1.1 PLASMA
Valid equations:
(Obtained from the
LaPlace transforms
derived from the
appropriate models
derived from the
pharmacokinetic
descriptions of the drug)
(EQ 4-1)
(EQ 4-2)
(EQ 4-3)
(EQ 4-4)
(EQ 4-5)
(EQ 4-6)
(EQ 4-7)
(EQ 4-8)
(EQ 4-9)
Utilization:
Can you determine the
slope and intercept from
a graph? Plot the data
in table 4 -1.on semi-log
graph paper. Extrapo-
late the line back to time
= 0 to get Cp
0
. Find the
half life. Calculate the
elimination rate con-
stant.
• You should be able to plot a data set Concentration vs. time on semilog yielding a straight line
with slope = and an intercept of .
FIGURE 4-1.
C
p
ln K t C
p
0
ln + ⋅ – =
X ln K t X
0
ln + ⋅ – =
C
p
C
p0
e
Kt –
=
C
p
0
D
V
d
------ =
t
½
0.693
K
------------- =
AUC Cp t d
0
∞ ( )

= Σ
Cp
n
Cp
n 1 +
+ ( )
2
------------------------------------- ∆t ⋅
. ,
| `
Cp
last
K
-------------- + =
AUMC t C ⋅ p t d
t
n
Cp
n
⋅ ( ) t
n 1 +
Cp
n 1 +
⋅ ( ) +
2
-------------------------------------------------------------------- ∆t ⋅
. ,
| `
0
t

Cp
l ast
K
2
---------------
t
l ast
Cp
last
⋅ ( )
K
---------------------------------- + + =
0
∞ ( )

=
MRT
AUMC
AUC
------------------ =
Cl K V
d
⋅ =
TABLE 4-1 Nifedipine 25 mg IV bolus
Time (hr)
Cp
(mcg/L)
2 139
4 65.6
6 31.1
8 14.6
K – C
p0
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-3
like this?
FIGURE 4-1 Nifedipine IV Bolus (25 mg IV Bolus)
• You should be able to determine K. A plot of the data in TABLE 4-1 results in FIGURE 4-1
Remember from high school algebra, the slope of any straight line is the rise over the run, ,
In the case of semi-log graphs dy is the difference in the logarithms of the concentrations. Thus,
using the rules of logarithms, when two logs are subtracted, the numbers themselves are
divided. i.e. . Thus if we are judicious in the concentrations that we
take, we can set the rise to a constant number. So, if we take any two concentrations such that
one concentration is half of the other (In FIGURE 4-1 above, we took 100 and 50), the time it
takes for the concentration to halve is the half life (in the graph above, 1.85 hr). Then
• You should be able to determine :. To do this, extrapolate the line to . The value of
when is (in the graph above, which is equal to for an IV bolus
dose only.
Thus,
The volume of distribution is a mathematical construct. It is merely the proportionality constant
between two knowns - the which results from a given . It is, however, useful because it
is patient specific and therefore can be used to predict how the patient will treat a subsequent
dose of the same drug. You should be able to obtain the volume of distribution from graphical
analysis of the data. Pay attention to the units! Make sure that they are consistent on both sides
of the equation. NOTE: the volume of distribution is not necessarily any physiological space.
For example the approximate volume of distribution of digoxin is about 600 L If that were a
physiological space and I were all water, that would mean that I would weigh about 1320
pounds. I’m a little overweight (I prefer to think that I’m underheight), but REALLY!
• Given any three of the variables of the IV bolus equation, either by direct information (the vol-
ume of distribution is such and such) or by graphical data analysis, you should be able to find
the fourth.
0 2 4 6 8
Time (hours)
101
102
103
C
o
n
c
e
n
t
r
a
t
i
o
n

(
n
g
/
m
L
)

-K1 = -0.375 hr
-1
C
p0
= 295 mic/L

C
o
n
c
e
n
t
r
a
t
i
o
n

(
m
i
c
/
L
)
Time (hr)
1.85 hr
100
50
dy
dx
------
C1 ( ) ln C2 ( ) ln –
C1
C2
-------
. ,
| `
ln =
K
0.693
t
½
-------------
0.693
1.85hr
---------------- 0.375 hr
1 –
= = =
V
d
t 0 = C
p
t 0 = C
p0
C
p0
295
mic
L
--------- = D V
d

Cp
0
Dose
V
d
------------- V
d
Dose
Cp
0
-------------
25mg
295mic
L
------------------
------------------ =
1000mic
mg
--------------------- 85L = ⋅ = , =
C
p0
D
0
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-4
• You should be able to calculate Area Under the Curve (AUC) from IV Bolus data (Time vs. Cp).
From the above data in TABLE 4-1 the AUC is calculated using (EQ 4-6):
which in this case is:
or
. In tabular format, the AUC calculation
is shown in TABLE 4-2.
The AUC of a plot of plasma concentration vs. time, in linear pharmacokinetics, is a number
which is proportional to the dose of the drug which gets into systemic circulation. The propor-
tionality constant, as before, is the volume of distribution. It is useful as a tool to compare the
amount of drug obtained by the body from different routes of administration or from the same
route of administration by dosage forms made by different manufacturers (calculate bioavail-
ability in subsequent discussions).
The AUC of a plot of Rate of Excretion of a drug vs. time, in linear pharmacokinetics, is the
mass of drug excreted into the urine, directly.
• You should be able to calculate the AUMC from IV Bolus data (Time vs. Cp). The equation for
AUMC is equation 4-7:
which in the
data given in TABLE 4-1 is:
+
TABLE 4-2 AUC
TIME Cp
0 295
2 139 434.0 434.0
4 65.6 204.6 638.6
6 31.1 96.7 735.3
8 14.6 45.7 781.0
0 38.9 819.9
AUC Cp t d
0
∞ ( )

= Σ
Cp
n
Cp
n 1 +
+
∆t
---------------------------------
. ,
| `
Cp
l
K
-------- + =
Σ
Cp
o
Cp
1
+
2
-------------------------- ∆t
1
Cp
1
Cp
2
+
2
-------------------------- ∆t
2
Cp
2
Cp
3
+
2
-------------------------- ∆t
3
Cp
3
Cp
last
+
2
------------------------------- ∆t
last
Cp
l ast
K1
--------------- + ⋅ + ⋅ + ⋅ + ⋅
¹ ¹
' '
¹ ¹
Σ
295 139 +
2
------------------------ 2 ⋅
139 65.6 +
2
------------------------- 2 ⋅
65.6 31.1 +
2
--------------------------- 2 ⋅
31.1 14.6 +
2
--------------------------- 2 ⋅
14.6
0.375
------------- + + + +
¹ ¹
' '
¹ ¹mcg
L
---------- hr
Σ 434 204.6 96.7 45.7 38.9 + + + + { ¦
mcg
L
---------- hr 819.9
mcg
L
---------- hr =
AUC
t 1 –
t
AUC
0
t

AUMC t C ⋅ p t d
t
n
Cp
n
⋅ ( ) t
n 1 +
Cp
n 1 +
⋅ ( ) +
2
-------------------------------------------------------------------- ∆t ⋅
. ,
| `
0
t

Cp
l ast
K
2
---------------
t
l ast
Cp
last
⋅ ( )
K
---------------------------------- + + =
0
∞ ( )

=
Σ
T
0
C ⋅ p
o
T
1
C ⋅ p
1
+
2
----------------------------------------------- ∆t
1
T
1
C ⋅ p
1
T
2
C ⋅ p
2
+
2
----------------------------------------------- ∆t
2
T
2
C ⋅ p
2
T
3
C ⋅ p
3
+
2
----------------------------------------------- ∆t
3
⋅ + ⋅ + ⋅
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-5
and thus,
+
or
Thus in tabular format the AUMC for data given in TABLE 4-1 is TABLE 4-3 below.
The AUMC is the Area Under the first Moment Curve. A plot of T*Cp vs. T is the first
moment curve. The time function buried in this plot, the Mean Residence Time (MRT), can be
extracted using equation 4-8 below.
It is the geometric mean time that the molecules of drug stay in the body. It has utility in the fact
that, as drug moves from the dosage form into solution in the gut, from solution in the gut into
the body, and from the body out, each process is cumulatively additive. That means if we can
physically separate each of these processes in turn, we can calculate the MRT of each process.
The MRT of each process is the the inverse of the rate constant for that process.
• You should be able to calculate MRT from IV Bolus data (Time vs. Cp) using equation 4-8
Since there is only the process of elimination (no release of the drug from the dosage form, no
absorption), the MRT is the inverse of the elimination rate constant, K. Thus MRT = 1/K.
TABLE 4-3 AUMC
TIME Cp Cp*T
0 295 0
2 139 278 278.0 278.0
4 65.6 262.4 540.4 818.4
6 31.1 186.6 449.0 1267.4
8 14.6 116.8 303.4 1570.8
0 0 415.3 1986.1
T
3
C ⋅ p
3
T
last
C ⋅ p
last
+
2
---------------------------------------------------------- ∆t
l ast
T
last
C ⋅ p
l ast
K
-------------------------------
Cp
last
K
2
--------------- + + ⋅
Σ
0 295 ⋅ 2 139 ⋅ +
2
--------------------------------------- 2 ⋅
2 139 ⋅ 4 65.6 ⋅ +
2
---------------------------------------- 2 ⋅
4 65.6 ⋅ 6 31.1 ⋅ +
2
------------------------------------------ 2 ⋅ + +
¹ ¹
' '
¹ ¹mcg
L
---------- hr
2
6 31.1 ⋅ 8 14.6 ⋅ +
2
------------------------------------------ 2 ⋅
8 14.6 ⋅
0.375
------------------
14.6
0.375
2
---------------- + +
¹ ¹
' '
¹ ¹
mcg
L
----------hr
2
Σ 278 540.4 449 303.4 311.47 103.82 + + + + + { ¦ 1986.1
mcg
L
---------- hr
2
=
AUMC
t
AUMC
0
t

MRT
AUMC
AUC
------------------ =
1986.1
819.9
---------------- 2.42 = =
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-6
Flow Chart 4-1 IV Bolus
Suppose the drug were given in a solution. Then the drug would have to be absorbed and then
eliminated. Since the MRTs are additive, the MRT of the oral solution would be made up of the
MRTs of the two processes, thus:
Flow Chart 4-2 Oral Solution
Consequently, if a drug has to be released from a dosage form for the drug to get into solution
which is subsequently absorbed, a tablet for example, the MRT of the tablet will consist of the
MRT(IV) and the MAT(os) and the Mean Dissolution Time (MDT), thus:
Flow Chart 4-3 Tablet
X
K
MRT(IV) = 1/K
K Ka
Xa
MRT(os) = MAT(os)+MRT(IV)
MRT(os) = 1/Ka + 1/K
X
X Xa Xd
Kd Ka K
MRT(tab) = MDT + MAT(os) + MRT(IV)
MRT(tab) = 1/Kd + 1/Ka + 1/K
MRT(tab) = MAT(tab) + MRT(IV)
MRT(tab) = 1/Ka (apparent) + 1/K
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-7
Normally, we don’t have information from the oral solution, just IV and tablet. So in that case
the information obtained about absorption from the tablet is bundled together into an apparent
absorption rate constant consisting of both dissolution and absorption.
It should be apparent that this is a reasonably easily utilized and powerful tool used to obtain
pharmacokinetic parameters.
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-8
4.1.2 IV BOLUS, PARENT COMPOUND, PLASMA PROBLEMS
Equations used in this
section:
1. from equation 4-3
2. equation 4-5
3. equation 4-8
4. = the y-intercept of the line from equation 4-3
5. Estimate for AUC = which is

Trapezoidal rule applied to equation 4-6
6. Estimate for AUMC = from equation 4-8

from equation 4-7
7. from equation 4-4
8.
K slope – =
t
1 2 ⁄
2 ln
K
-------- =
MRT
1
K
--- - estimate ( ) = MRT
AUMC
AUC
------------------ =
Cp
0
AUC
Cp
0
K
--------- = Cp t d
0

AUC Cp t d
0
∞ ( )

= Σ
Cp
n
Cp
n 1 +
+ ( )
2
-------------------------------------
. ,
| `
∆t ( )
Cp
last
K
-------------- + =
AUMC AUC MRT ⋅ =
AUMC Cp t d
t
n
Cp
n
⋅ ( ) t
n 1 +
Cp
n 1 +
⋅ ( ) +
2
-------------------------------------------------------------------- ∆t
n

. ,
| `
0
t

Cp
last
K
2
---------------
t
last
Cp
l ast
⋅ ( )
K
---------------------------------- + + =
0
∞ ( )

V
d
Dose
Cp
0
------------- =
Cl K1 V
d
Cp
0
AUC
------------
Dose
Cp
0
------------- ⋅ = ⋅
Dose
AUC
------------- = =
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-9
Acyclovir (Problem 4 - 1)
De Miranda and Burnette, “Metabolic Fate and Pharmacokinetics of the Acyclovir Prodrug Valaciclovir in Cynomolgus Mon-
keys”, Drug Metabolism and Disposition (1994): 55-59.
Acyclovir is an antiviral drug used in the treatment of herpes simplex, varicella zoster, and in suppressive therapy. In
this study, three male cynomolgus monkeys were each given a 10 intravenous dose. The monkeys weighed an
average of 3.35 each. Blood samples were collected and the following data was obtained:
From the data presented in the Preceding table, determine the following:
1. Find the elimination rate constant, .
2. Find the half life, .
3. Find .
4. Find .
5. Find the Area Under the Curve, .
6. Find the area under the first moment curve, .
7. Find the volume of distribution,
8. Find the clearance, .
Problem Submitted By: Maya Lyte AHFS 12:34.56 Antivirals
Problem Reviewed By: Vicki Long GPI: 1234567890 Antivirals
PROBLEM TABLE 4 - 1. Acyclovir
Time (hours)
Serum concentration
0.167 26.0
0.300 23.0
0.500 19.0
0.75 16.0
1.0 12.0
1.5 7.0
2.0 5.0
mg kg ⁄
kg
µg mL ⁄ ( )
k
t
½
MRT
C
p
( )
0
AUC
AUMC
V
d
Cl
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-10
(Problem 4 - 1) Acyclovir:
1.
2. .
3. .
4. .
5. .
6. .
7.
8. .

0.5 1.0 1.5 2.0
10
10
10
0.0
0
1
2
C
O
N
C
E
N
T
R
A
T
I
O
N

(
M
I
C
/
M
L
)
TIME (HR)
k 0.93hr
1 –
=
t
½
0.75hr =
MRT 1.08hr =
C
p
( )
0
30.4ug mL ⁄ =
AUC 32.75ug mL hr ⋅ ⁄ =
AUMC 35.2ug mL ⁄ hr
2
⋅ =
V
d
1.1L =
Cl 1.02L hr ⁄ =
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-11
Aluminum (Problem 4 - 2)
Xu, Pai, and Melethil, "Kinetics of Aluminum in Rats. II: Dose-Dependent Urinary and Biliary Excretion", Journal of Pharmaceu-
tical Sciences, Oct 1991, p 946 - 951.
A study by Xu, Pai, and Melethil establishes the pharmacokinetics of Aluminum in Rats. In this study, four rats with an
average weight of 375g, were given an IV bolus dose of aluminum (1 mg/kg). Blood samples were taken at various
intervals and the following data was obtained:
From the data presented in the preceding table, determine the following:
1. Find the elimination rate constant, .
2. Find the half life, .
3. Find .
4. Find .
5. Find the Area Under the Curve, .
6. Find the area under the first moment curve, .
7. Find the volume of distribution,
8. Find the clearance, .
Problem Submitted By: Maya Lyte AHFS 12:34.56 Antivirals
Problem Reviewed By: Vicki Long GPI: 1234567890 Antivirals
PROBLEM TABLE 4 - 2. Aluminum
Time (hours)
Serum concentration,
0.4 19000
0.6 18000
1.4 15000
1.6 14500
2.3 12500
3.0 10500
4.0 8500
5.0 6500
6.0 5000
8.0 3250
10.0 2000
12.0 1250
ng
mL
--------
k
t
½
MRT
C
p
( )
0
AUC
AUMC
V
d
Cl
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-12
(Problem 4 - 2) Aluminum:
1.
2. .
3. .
4. .
5. .
6. .
7.
8. .

0 2 4 6 8 12
10
10
10
10
TIME (HR)
C
O
N
C
E
N
T
R
A
T
I
O
N

(
N
G
/
M
L
)
3
4
5
k 0.234hr
1 –
=
t
½
3hr =
MRT 4.3hr =
C
p
( )
0
21000ng mL ⁄ =
AUC 89285ng mL hr ⋅ ⁄ =
AUMC 383926ng mL hr
2
⋅ ⁄ =
V
d
17.86mL =
Cl 4.18mL hr ⁄ =
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-13
Amgen (Problem 4 - 3)
Salmonson, Danielson, and Wikstrom, "The pharmacokinetics of recombinant human erythropoetin after intravenous and subcuta-
neous administration to healthy subjects", Br. F. clin. Pharmac. (1990), p 709- 713.
Amgen (r-Epo) is a form of recombinant erythropoetin. Erythropoetin is a hormone that is produced in the kidneys and
used in the production of red blood cells. The kidneys of patients who have end-stage renal failure cannot produce
erythropoetin; therefore, r-Epo is being investigated for use in these patients in order to treat the anemia that results
from the lack of erythropoetin. In a study by Salmonson et al, six healthy volunteers were used to demonstrate that
both IV and subcutaneous administration of erythropoetin have similar effects in the treatment of anemia due to
chronic renal failure. The six volunteers were each given a 50 U/kg intravenous dose of Amgen. The average weight
of the six volunteers was 79 kg. Blood samples were drawn at various times and the data obtained is summarized
below:
From the data presented in the preceding table, determine the following:
1. Find the elimination rate constant, .
2. Find the half life, .
3. Find .
4. Find .
5. Find the Area Under the Curve, .
6. Find the area under the first moment curve, .
7. Find the volume of distribution,
8. Find the clearance, .
Problem Submitted By: Maya Lyte AHFS 12:34.56 Antivirals
Problem Reviewed By: Vicki Long GPI: 1234567890 Antivirals
PROBLEM TABLE 4 - 3. Amgen
Time (hours)
Serum concentration,
2 700
4 600
6 400
8 300
12 150
24 40
mU
mL
---------
k
t
½
MRT
C
p
( )
0
AUC
AUMC
V
d
Cl
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-14
(Problem 4 - 3) Amgen:
1.
2. .
3. .
4. .
5. .
6. .
7.
8. .
0 5 10 15 20 25
10
1
10
2
10
3
C
o
n

(
m
U
/
m
L
)

TIME (HR)
C
O
N
C
E
N
T
R
A
T
I
O
N

(
M
U
/
M
L
)
k 0.134hr
1 –
=
t
½
5.2hr =
MRT 7.46hr =
C
p
( )
0
900mU mL ⁄ =
AUC 6945mU mL hr ⋅ ⁄ =
AUMC 49600 = mU mL hr
2
⋅ ⁄
V
d
4.44L =
Cl 0.6L hr ⁄ =
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-15
Atrial Naturetic Peptide (ANP) (Problem 4 - 4)
Brier and Harding, "Pharmacokinetics and Pharmacodynamics of Atrial Naturetic Peptide after Bolus and Infusion Administra-
tion in the Isolated Perfused Rat Kidney", The Journal of Pharmacology and Experimental Therapeutics (1989), p 372 - 377.
A study by Brier and Harding a dose of 45 ng was given by IV bolus to rats. Samples of blood were taken at various
intervals throughout the length of the study and the following data was obtained:
From the data presented in the preceding table, determine the following:
1. Find the elimination rate constant, .
2. Find the half life, .
3. Find .
4. Find .
5. Find the Area Under the Curve, .
6. Find the area under the first moment curve, .
7. Find the volume of distribution,
8. Find the clearance, .
Problem Submitted By: Maya Lyte AHFS 12:34.56 Antivirals
Problem Reviewed By: Vicki Long GPI: 1234567890 Antivirals
PROBLEM TABLE 4 - 4. Atrial Naturetic Peptide (ANP)
Time (minutes)
Serum concentration,
3 380
10 280
20 170
30 130
40 100
50 70
60 50
pg
mL
--------
k
t
½
MRT
C
p
( )
0
AUC
AUMC
V
d
Cl
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-16
(Problem 4 - 4) Atrial Naturetic Peptide (ANP):
1.
2. .
3. .
4. .
5. .
6. .
7.
8. .
0 10 20 30 40 50 60
Time (min)
10
1
10
2
10
3
C
o
n

(
p
g
/
m
L
)

C
O
N
C
E
N
T
R
A
T
I
O
N

(
P
G
/
M
L
)
k 0.0345min
1 –
=
t
½
20.09min =
MRT 28.95min =
C
p
( )
0
386.6pg mL ⁄ =
AUC 11206.4pg mL ⁄ min ⋅ =
AUMC 324425.4pg mL ⁄ min
2
⋅ =
V
d
116.4mL =
Cl 4.02mL min ⁄ =
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-17
Aztreonam (Problem 4 - 5)
Cuzzolim et al., "Pharmacokinetics and Renal Tolerance of Aztreonam in Premature Infants", Antimicrobial Agents and Chemo-
therapy (Sept. 1991), p. 1726 - 1928.
Aztreonam is a monolactam structure which is active against aerobic, gram-negative bacilli. The pharmacokinetic
parameters of Aztreonam were established in a study presented in by Cuzzolim et al in which Aztreonam (100 mg/ kg)
was administered intravenously to 30 premature infants over 3 minutes every 12 hours. The group of neonates had an
average weight of 1639.6g. The following set of data was obtained:
From the data presented in the preceding table, determine the following:
1. Find the elimination rate constant, .
2. Find the half life, .
3. Find .
4. Find .
5. Find the Area Under the Curve, .
6. Find the area under the first moment curve, .
7. Find the volume of distribution,
8. Find the clearance, .
Problem Submitted By: Maya Lyte AHFS 12:34.56 Antivirals
Problem Reviewed By: Vicki Long GPI: 1234567890 Antivirals
PROBLEM TABLE 4 - 5. Aztreonam
Time (minutes)
Serum concentration,
1 40.50
2 34.99
3 29.99
4 23.88
5 22.20
6 19.44
7 16.55
8 14.99
µg
mL
--------
k
t
½
MRT
C
p
( )
0
AUC
AUMC
V
d
Cl
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-18
(Problem 4 - 5) Aztreonam:
1.
2. .
3. .
4. .
5. .
6. .
7.
8. .
0 2 4 6 8
10
1
10
2
C
o
n

(
u
g
/
m
L
)

TIME (MIN)
C
O
N
C
E
N
T
R
A
T
I
O
N

(
U
G
/
M
L
)
k 0.144min
1 –
=
t
½
4.81min =
MRT 6.94min =
C
p
( )
0
45.75ug mL ⁄ =
AUC 317.7ug mL min ⋅ ⁄ =
AUMC 2204.8ug mL min ⋅ ⁄
2
=
V
d
3.58L =
Cl 0.516L min ⁄ =
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-19
Recombinant Bovine Placental Lactogen (Problem 4 - 6)
Byatt, et. al., "Serum half-life and in-vivo actions of recombinant bovine placental lactogen in the dairy cow", Journal of Endocri-
nology (1992), p. 185 - 193.
Bovine placental lactogen (bPL) is a hormone similar to growth hormone and prolactin. It binds to both prolactin and
growth hormone receptors in the rabbit and stimulates lactogenesis in the rabbit. In a study by Byatt, et. al., four cows
(2 pregnant and 2 nonpregnant) were given IV bolus injections of 4 mg and the following data was obtained:
From the data presented in the preceding table, determine the following:
1. Find the elimination rate constant, .
2. Find the half life, .
3. Find .
4. Find .
5. Find the Area Under the Curve, .
6. Find the area under the first moment curve, .
7. Find the volume of distribution,
8. Find the clearance, .
Problem Submitted By: Maya Lyte AHFS 12:34.56 Antivirals
Problem Reviewed By: Vicki Long GPI: 1234567890 Antivirals
PROBLEM TABLE 4 - 6. Recombinant Bovine Placental Lactogen
Time (minutes)
Serum concentration
3.8 117
6.8 72
12.0 43
16.0 27
20.0 18
µg
L
------
k
t
½
MRT
C
p
( )
0
AUC
AUMC
V
d
Cl
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-20
(Problem 4 - 6) Recombinant Bovine Placental Lactogen:
1.
2. .
3. .
4. .
5. .
6. .
7.
8. .
0 5 10 15 20
Time (min)
10
1
10
2
10
3
C
o
n

(
u
g
/
L
)

C
O
N
C
E
N
T
R
A
T
I
O
N

(
M
I
C
/
L
)
k 0.113min
1 –
=
t
½
6.13min =
MRT 8.85min =
C
p
( )
0
167.8ug L ⁄ =
AUC 1484.9ug L min ⋅ ⁄ =
AUMC 13141.1ug L min ⋅ ⁄
2
=
V
d
23.84L =
Cl 2.69L min ⁄ =
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-21
Caffeine (Problem 4 - 7)
Dorrbecker et. al., "Caffeine and Paraxanthine Pharmacokinetics in the Rabbit: Concentration and Product Inhibition Effects.",
Journal of Pharmacokinetics and Biopharmaceutics (1987), p.117 - 131.
This study examines the pharmacokinetics of caffeine in the rabbit. In this study type I New Zealand White rabbits
were given an 8 mg intravenous dose of caffeine. Blood samples were taken and the following data was obtained:
From the data presented in the preceding table, determine the following:
1. Find the elimination rate constant, .
2. Find the half life, .
3. Find .
4. Find .
5. Find the Area Under the Curve, .
6. Find the area under the first moment curve, .
7. Find the volume of distribution,
8. Find the clearance, .
Problem Submitted By: Maya Lyte AHFS 12:34.56 Antivirals
Problem Reviewed By: Vicki Long GPI: 1234567890 Antivirals
PROBLEM TABLE 4 - 7. Caffeine
Time (minutes)
Serum concentration
12 3.75
40 2.80
65 2.12
90 1.55
125 1.23
173 0.72
243 0.37
µg
mL
--------
k
t
½
MRT
C
p
( )
0
AUC
AUMC
V
d
Cl
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-22
(Problem 4 - 7) Caffeine:
1.
2. .
3. .
4. .
5. .
6. .
7.
8. .
0 50 100 150 200 250
Time (min)
10
-1
10
0
10
1
C
o
n

(
u
g
/
L
)

Caffeine
C
O
N
C
E
N
T
R
A
T
I
O
N

(
M
I
C
/
M
L
)
k 0.00997min
1 –
=
t
½
69.51min =
MRT 100.3min =
C
p
( )
0
4.105ug mL ⁄ =
AUC 411.7ug mL ⁄ min ⋅ =
AUMC 41293.5ug mL ⁄ min
2
⋅ =
V
d
1.95L =
Cl 19.44mL min ⁄ =
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-23
Ceftazidime (Problem 4 - 8)
Demotes-Mainard, et. al., "Pharmacokinetics of Intravenous and Intraperitoneal Ceftazidime in Chronic Ambulatory Peritoneal
Dyialysis", Journal of Clinical Pharmacology (1993), p. 475 - 479.
Ceftazidime is a third generation cephalosporin which is administered parenterally. In this study, eight patients with
chronic renal failure were each given 1 g of ceftazidime intravenously. Both blood samples were taken the data
obtained from the study is summarized in the following table:
From the data presented in the preceding table, determine the following:
1. Find the elimination rate constant, .
2. Find the half life, .
3. Find .
4. Find .
5. Find the Area Under the Curve, .
6. Find the area under the first moment curve, .
7. Find the volume of distribution,
8. Find the clearance, .
Problem Submitted By: Maya Lyte AHFS 12:34.56 Antivirals
Problem Reviewed By: Vicki Long GPI: 1234567890 Antivirals
PROBLEM TABLE 4 - 8. Ceftazidime
Time (hours)
Serum concentration
1 50
2 45
4 38
24 21
36 14
48 11
60 8
72 4
mg
L
-------
k
t
½
MRT
C
p
( )
0
AUC
AUMC
V
d
Cl
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-24
(Problem 4 - 8) Ceftazidime:
1.
2. .
3. .
4. .
5. .
6. .
7.
8. .
0 20 40 60 80
Time (hours)
10
0
10
1
10
2
C
o
n

(
m
g
/
L
)

C
O
N
C
E
N
T
R
A
T
I
O
N

(
M
G
/
L
)
k 0.0324hr
1 –
=
t
½
21.39hr =
MRT 30.86hr =
C
p
( )
0
47.57mg L ⁄ =
AUC 1468.2mg L hr ⋅ ⁄ =
AUMC 45308.6mg L hr ⋅ ⁄
2
=
V
d
21.02L =
Cl 0.681L hr ⁄ =
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-25
Ciprofloxacin (Problem 4 - 9)
Lettieri, et. al., "Pharmacokinetic Profiles of Ciprofloxacin after Single Intravenous and Oral Doses", Antimicrobial Agents and
Chemotherapy (May 1992), p. 993 -996.
Ciprofloxacin is a fluoroquinolone antibiotic which is used in the treatment of infections of the urinary tract, lower res-
piratory tract, skin, bone, and joint. In this study, twelve healthy, male volunteers were each given 300 mg intravenous
doses of Ciprofloxacin. Blood and urine samples were collected at various times throughout the day and the following
data was collected:
From the data presented in the preceding table, determine the following:
1. Find the elimination rate constant, .
2. Find the half life, .
3. Find .
4. Find .
5. Find the Area Under the Curve, .
6. Find the area under the first moment curve, .
7. Find the volume of distribution,
8. Find the clearance, .
Problem Submitted By: Maya Lyte AHFS 12:34.56 Antivirals
Problem Reviewed By: Vicki Long GPI: 1234567890 Antivirals
PROBLEM TABLE 4 - 9. Ciprofloxacin
Time (hours)
Serum concentration
2 1.20
3 0.85
4 0.70
6 0.50
8 0.35
10 0.25
mg
L
-------
k
t
½
MRT
C
p
( )
0
AUC
AUMC
V
d
Cl
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-26
(Problem 4 - 9) Ciprofloxacin:
1.
2. .
3. .
4. .
5. .
6. .
7.
8. .
0 2 4 6 8 10
Time (hours)
10
-1
10
0
10
1
C
o
n

(
m
g
/
L
)

C
O
N
C
E
N
T
R
A
T
I
O
N

(
M
G
/
L
)
k 0.1875hr
1 –
=
t
½
3.7hr =
MRT 5.33hr =
C
p
( )
0
1.57mg L ⁄ =
AUC 8.395mg L hr ⋅ ⁄ =
AUMC 44.74mg L hr ⋅ ⁄
2
=
V
d
190.6L =
Cl 35.74L hr ⁄ =
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-27
The effect of Probenecid on Diprophylline (DPP) (Problem 4 - 10)
Nadai et al, "Pharmacokinetics and the Effect of Probenecid on the Renal Excretion Mechanism of Diprophylline", Journal of
Pharmaceutical Sciences (Oct 1992), p. 1024 - 1027.
Diprophylline is used as a bronchodilator. A study by Nadai et al was designed to determine whether or not coadmin-
istration of Diprophylline with Probenecid affected the pharmacokinetic parameters of Diprophylline. In this study,
male rats (average weight: 300 g) were given 60 mg/kg of Diprophylline intravenously and a 3 mg/kg loading dose of
Probenecid followed by a continuous infusion of 0.217 mg/min/kg of Probenecid. The following set of data was
obtained for Diprophylline (DPP):
From the data presented in the preceding table, determine the following:
1. Find the elimination rate constant, .
2. Find the half life, .
3. Find .
4. Find .
5. Find the Area Under the Curve, .
6. Find the area under the first moment curve, .
7. Find the volume of distribution,
8. Find the clearance, .
Problem Submitted By: Maya Lyte AHFS 12:34.56 Antivirals
Problem Reviewed By: Vicki Long GPI: 1234567890 Antivirals
PROBLEM TABLE 4 - 10. The effect of Probenecid on Diprophylline (DPP)
Time (minutes)
Serum concentration
16 40.00
31 27.00
60 13.00
91 6.50
122 3.50
µg
mL
--------
k
t
½
MRT
C
p
( )
0
AUC
AUMC
V
d
Cl
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-28
(Problem 4 - 10) The effect of probenecid on diprophylline (DPP):
1.
2. .
3. .
4. .
5. .
6. .
7.
8. .
0 20 40 60 80 100
Time (min)
10
0
10
1
10
2
C
o
n

(
u
g
/
m
L
)

C
O
N
C
E
N
T
R
A
T
I
O
N

(
M
I
C
/
M
L
)
k 0.023min
1 –
=
t
½
30.13min =
MRT 43.48min =
C
p
( )
0
55.13ug mL ⁄ =
AUC 2396.96ug mL min ⋅ ⁄ =
AUMC 104219.8ug mL min ⋅ ⁄
2
=
V
d
326.5mL =
Cl 7.5mL min ⁄ =
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-29
Epoetin (Problem 4 - 11)
MacDougall et. al., "Clinical Pharmacokinetics of Epoetin (Recombinant Human Erythropoetin", Clinical Pharmacokinetics
(1991), p 99 - 110.
Epoetin is recombinant human erythropoetin. Erythropoetin is a hormone that is produced in the kidneys and used in
the production of red blood cells. The kidneys of patients who have end-stage renal failure cannot produce erythropo-
etin; therefore, Epoetin is used in these patients to treat the anemia that results from the lack of erythropoetin. Epoetin
has also been used in the treatment of anemias resulting from AIDS. malignant disease, prematurity, rheumatoid arthri-
tis, sickle-cell anemia, and myelosplastic syndrome. In a study by Macdougall et al, eight patients who were on perito-
neal dialysis (CAPD) were given an IV bolus dose of 120 U/kg which decayed monoexponentially from a peak of 3959
U/L to 558 U/L at 24 hours. The following data was obtained:
From the data presented in the preceding table and assuming that the patient weighs 65 kg, determine the following:
1. Find the elimination rate constant, .
2. Find the half life, .
3. Find .
4. Find .
5. Find the Area Under the Curve, .
6. Find the area under the first moment curve, .
7. Find the volume of distribution,
8. Find the clearance, .
Problem Submitted By: Maya Lyte AHFS 12:34.56 Antivirals
Problem Reviewed By: Vicki Long GPI: 1234567890 Antivirals
PROBLEM TABLE 4 - 11. Epoetin
Time (hours)
Serum concentration
0.0 4000
0.5 3800
1.0 3600
2.0 3300
3.0 3000
4.0 2550
5.0 2350
6.0 2150
7.0 1900
U
L
----
k
t
½
MRT
C
p
( )
0
AUC
AUMC
V
d
Cl
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-30
(Problem 4 - 11) Epoetin:
1.
2. .
3. .
4. .
5. .
6. .
7.
8. .
0 1 2 3 4 5 6 7
Time (hours)
10
3
10
4
C
o
n

(
U
/
L
)

C
O
N
C
E
N
T
R
A
T
I
O
N

(
U
/
L
)
k 0.107 hr
1 –
=
t
½
6.5 hr =
MRT 9.38 hr =
C
p
( )
0
4023 Units/L =
AUC 37775
Units hr ⋅
L
------------------------ =
AUMC 354697
Units hr
2

L
--------------------------- =
V
d
1.9 L =
Cl 0.2065
L
hr
----- =
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-31
Famotidine (Problem 4 - 12)
Kraus, et. al., "Famotidine--Pharmacokinetic Properties and Suppression of Acid Secretion in Pediatric Patients Following Car-
diac Surgery", Clinical Pharmacokinetics (1990), p 77 - 80.
Famotidine is a histamine H2-receptor antagonist. The study by Kraus, et. al., focuses on the kinetics of famotidine in
children. In the study, ten children with normal kidney function and a body weight ranging from 14 - 25 kg, were each
given a single intravenous 0.3 mg/kg dose of famotidine. Blood and urine samples were taken providing the following
data:
From the data presented in the preceding table, determine the following assuming that the patient weighs 17.2 kg:
1. Find the elimination rate constant, .
2. Find the half life, .
3. Find .
4. Find .
5. Find the Area Under the Curve, .
6. Find the area under the first moment curve, .
7. Find the volume of distribution,
8. Find the clearance, .
Problem Submitted By: Maya Lyte AHFS 12:34.56 Antivirals
Problem Reviewed By: Vicki Long GPI: 1234567890 Antivirals
PROBLEM TABLE 4 - 12. Famotidine
Time (hours)
Serum concentration
0.33 300
0.50 250
1.00 225
4.00 125
8.00 70
12.00 40
16.00 15
µg
L
------
k
t
½
MRT
C
p
( )
0
AUC
AUMC
V
d
Cl
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-32
(Problem 4 - 12) Famotidine:
1.
2. .
3. .
4. .
5. .
6. .
7.
8. .
0 5 10 15 20
Time (hours)
10
1
10
2
10
3
C
o
n

(
u
g
/
m
L
)

C
O
N
C
E
N
T
R
A
T
I
O
N

(
M
I
C
/
L
)
k 0.17 hr
1 –
=
t
½
3.9 hr =
MRT 5.7 hr =
C
p
( )
0
285
µg
L
------ =
AUC 1600
µg hr ⋅
L
----------------- =
AUMC 9000
µg hr
2

L
------------------ =
V
d
18 L =
Cl 3.2L =
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-33
Ganciclovir (Problem 4 - 13)
Trang, et. al., "Linear single-dose pharmacokinetics of ganciclovir in newborns with congenital cytomegalovirus infections", Clin-
ical Pharmacology and Therapeutics (1993), p. 15 - 21.
Ganciclovir (mw: 255.23) is used against the human herpes viruses, cytomegalovirus retinitis, and cytomegalovirus
infections of the gastrointestinal tract. In this study, twenty-seven newborns with cytomegalovirus disease were given
4 mg/kg of ganciclovir intravenously over one hour. Blood samples were taken and the data obtained is summarized in
the following table:
From the data presented in the preceding table and assuming the patient weighs 3.6 kg, determine the following :
1. Find the elimination rate constant, .
2. Find the half life, .
3. Find .
4. Find .
5. Find the Area Under the Curve, .
6. Find the area under the first moment curve, .
7. Find the volume of distribution,
8. Find the clearance, .
Problem Submitted By: Maya Lyte AHFS 12:34.56 Antivirals
Problem Reviewed By: Vicki Long GPI: 1234567890 Antivirals
PROBLEM TABLE 4 - 13. Ganciclovir
Time (hours) Serum concentration
1.50 4.50
2.00 4.00
3.00 3.06
4.00 2.40
6.00 1.45
8.00 0.87
k
t
½
MRT
C
p
( )
0
AUC
AUMC
V
d
Cl
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-34
(Problem 4 - 13) Ganciclovir:
1.
2. .
3. .
4. .
5. .
6. .
7.
8. .

0 2 4 6 8
10
10
10
C
O
N
C
E
N
T
R
A
T
I
O
N

(
M
I
C
M
O
L
E
/
L
)
TIME (HR)
k 0.288hr
1 –
=
t
½
2.4hr =
MRT 3.5hr =
C
p
( )
0
23
µmole
mL
---------------- =
AUC 80
µmole hr ⋅
mL
-------------------------- =
AUMC 280
µmole hr
2

mL
----------------------------- =
V
d
Dose
Cp
0
-------------
4
mg
kg
------- 3.6kg
1000µg
mg
------------------- ⋅ ⋅
23
µmole
L
---------------- 255.23
µg
µmole
---------------- ⋅
------------------------------------------------------------- 2.45L = = =
Cl 0.7
L
hr
----- =
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-35
Imipenem (Problem 4 - 14)
Heikkila, Renkonen, and Erkkola, "Pharmacokinetics and Transplacental Passage of Imipenem During Pregnancy", Antimicrobial
Agents and Chemotherapy (Dec. 1992), p 2652 - 2655.
Imipenem is a beta-lactam antibiotic which is used in combination with cilastin and is active against a broad spectrum
of bacteria. The pharmacokinetics of Imipenem in pregnant women is established in this study. Twenty women (six of
which were non-pregnant controls) were given a single intravenous dose of 500 mg of imipenem-cilastin (1:1). Blood
samples were taken at various intervals and the data obtained is summarized in the following table:
From the data presented in the preceding table, determine the following:
1. Find the elimination rate constant, .
2. Find the half life, .
3. Find .
4. Find .
5. Find the Area Under the Curve, .
6. Find the area under the first moment curve, .
7. Find the volume of distribution,
8. Find the clearance, .
Problem Submitted By: Maya Lyte AHFS 12:34.56 Antivirals
Problem Reviewed By: Vicki Long GPI: 1234567890 Antivirals
PROBLEM TABLE 4 - 14. Imipenem
Time (minutes)
Serum concentration
10 27.00
15 23.50
30 15.50
45 9.50
60 6.50
mg
L
-------
k
t
½
MRT
C
p
( )
0
AUC
AUMC
V
d
Cl
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-36
(Problem 4 - 14) Imipenem:
1.
2. .
3. .
4. .
5. .
6. .
7.
8. .

0 10 20 30 40 50 60
10
10
10
TIME (MIN)
C
O
N
C
E
N
T
R
A
T
I
O
N

(
M
G
/
L
)
1
2
0
k 0.029 min
1 –
=
t
½
24 min =
MRT 34.5 min =
C
p
( )
0
36.2
mg
L
------- =
AUC 1250
mg min ⋅
L
--------------------- =
AUMC 43125
mg min
2

L
------------------------ =
V
d
Dose
Cp
0
-------------
500mg
36.2
mg
L
-------
------------------ 13.8L = = =
Cl 0.4
L
min
--------- =
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-37
Methylprednisolone (Problem 4 - 15)
Patel, et. al., "Pharmacokinetics of High Dose Methylprednisolone and Use in Hematological Malignancies", Hematological
Oncology (1993), p. 89 - 96.
Methylprednisolone is a corticosteriod that has been used in combination chemotherapy for the treatment of hemato-
logical malignancy, myeloma, and acute lymphoblastic leukemia. In a study by Patel et. al., eight patients were given
1.5 gram intravenous doses of methylprednisolone from which the following data was obtained:
From the data presented in the preceding table, determine the following:
1. Find the elimination rate constant, .
2. Find the half life, .
3. Find .
4. Find .
5. Find the Area Under the Curve, .
6. Find the area under the first moment curve, .
7. Find the volume of distribution,
8. Find the clearance, .
Problem Submitted By: Maya Lyte AHFS 12:34.56 Antivirals
Problem Reviewed By: Vicki Long GPI: 1234567890 Antivirals
PROBLEM TABLE 4 - 15. Methylprednisolone
Time (hours)
Serum concentration
0.5 19.29
1.0 17.56
1.8 15.10
4.0 9.98
5.8 7.10
8.0 4.70
12.0 2.21
18.0 0.71
24.0 0.23
µg
mL
--------
k
t
½
MRT
C
p
( )
0
AUC
AUMC
V
d
Cl
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-38
(Problem 4 - 15) Methylprednisolone:
1.
2. .
3. .
4. .
5. .
6. .
7.
8. .
0 5 10 15 20 25
Time (hours)
10
-1
10
0
10
1
10
2
C
o
n

(
u
g
/
m
L
)

C
O
N
C
E
N
T
R
A
T
I
O
N

(
M
I
C
/
M
L
)
k 0.188 hr
1 –
=
t
½
3.69hr =
MRT 5.3hr =
C
p
( )
0
21.2
µg
mL
-------- =
AUC 112.5
µg hr ⋅
mL
----------------- =
AUMC 598.4
µg hr
2

mL
------------------ =
V
d
71L =
Cl 13.3
L
hr
----- =
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-39
Omeprazole (Problem 4 - 16)
Anderson, et. al., "Pharmacokinetics of [14C] Omeprazole in Patients with Liver Cirrhosis", Clinical Pharmacokinetics (1993), p.
71 - 78.
Omeprazole (mw: 345.42) is a gastric proton-pump inhibitor which decreases gastric acid secretion. It is effective in
the treatment of ulcers and esophageal reflux. In normal patients 80% of the omeprazole dose is excreted as metabo-
lites in the urine and the remainder is excreted in the feces. In the study by Anderson, et. al., eight patients with liver
cirrhosis were given 20 mg, IV bolus doses of omeprazole. The patients had a mean body weight of 70 kg. Both blood
were taken at various intervals throughout the study and the following data was obtained:
From the data presented in the preceding table, determine the following :
1. Find the elimination rate constant, .
2. Find the half life, .
3. Find .
4. Find .
5. Find the Area Under the Curve, .
6. Find the area under the first moment curve, .
7. Find the volume of distribution,
8. Find the clearance, .
Problem Submitted By: Maya Lyte AHFS 12:34.56 Antivirals
Problem Reviewed By: Vicki Long GPI: 1234567890 Antivirals
PROBLEM TABLE 4 - 16. Omeprazole
Time (hours)
Serum concentration
0.75 3.49
1.00 3.25
2.00 2.46
3.00 1.86
4.00 1.40
5.00 1.06
6.00 0.80
7.00 0.61
8.00 0.46
10.00 0.26
12.00 0.15
ρmole
mL
----------------
k
t
½
MRT
C
p
( )
0
AUC
AUMC
V
d
Cl
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-40
(Problem 4 - 16) Omeprazole:
1.
2. .
3. .
4. .
5. .
6. .
7.
8. .
0 2 4 6 8 10 12
Time (hours)
10
-1
10
0
10
1
C
o
n

(
u
m
o
l
/
m
L
)

C
O
N
C
E
N
T
R
A
T
I
O
N

(
P
I
C
O
M
O
L
E
/
M
L
)
k 0.280hr
1 –
=
t
½
2.5hr =
MRT 3.57hr =
C
p
( )
0
4.3
ρmole
mL
---------------- =
AUC 15.4
ρmole hr ⋅
mL
-------------------------- =
AUMC 55
ρmole hr
2

mL
----------------------------- =
V
d
Dose
Cp
0
-------------
20mg
4.3
ρmole
mL
----------------
mmole
10
9
ρmole
-------------------------
345.42mg
mmole
------------------------
1000mL
L
-------------------- ⋅ ⋅ ⋅
------------------------------------------------------------------------------------------------------------ 13465L = = =
Cl 3.9
L
hr
----- =
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-41
Pentachlorophenol (Problem 4 - 17)
Reigner, Rigod, and Tozer, "Absorption, Bioavailability, and Serum Protein Binding of Pentachlorophenol in the B6C3F1 Mouse",
Pharmaceutical Research (1992), p 1053 - 1057.
Pentachlorophenol (PCP) is a general biocide. That is, it is an insecticide, fungicide, bactericide, herbicide, algaecide,
and molluskicide, that is used as a wood preservative. Extensive exposure to PCP can be fatal. In a study by Reigner
et al, six mice (average weight: 27 g) were given 15 mg/kg of PCP by intravenous bolus. Blood samples were taken at
various intervals from which the following data was obtained:
From the data presented in the preceding table, determine the following :
1. Find the elimination rate constant, .
2. Find the half life, .
3. Find .
4. Find .
5. Find the Area Under the Curve, .
6. Find the area under the first moment curve, .
7. Find the volume of distribution,
8. Find the clearance, .
Problem Submitted By: Maya Lyte AHFS 12:34.56 Antivirals
Problem Reviewed By: Vicki Long GPI: 1234567890 Antivirals
PROBLEM TABLE 4 - 17. Pentachlorophenol
Time (hours)
Serum concentration
0.083 38.00
4.000 22.00
8.000 14.00
12.000 7.90
24.000 1.30
28.000 0.75
32.000 0.60
36.000 0.40
µg
mL
--------
k
t
½
MRT
C
p
( )
0
AUC
AUMC
V
d
Cl
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-42
(Problem 4 - 17) Pentachlorphenol:
1.
2. .
3. .
4. .
5. .
6. .
7.
8. .
0 10 20 30 40
Time (hours)
10
-1
10
0
10
1
10
2
C
o
n

(
u
g
/
m
L
)

C
O
N
C
E
N
T
R
A
T
I
O
N

(
M
I
C
/
M
L
)
k 0.134 hr
1 –
=
t
½
5.2hr =
MRT 7.5hr =
C
p
( )
0
35.6
µg
mL
-------- =
AUC 281
µg hr ⋅
mL
----------------- =
AUMC 2100
µg hr
2

mL
------------------- =
V
d
11.4mL =
Cl 1.5
ml
hr
------ =
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-43
9-(2-phophonylmethoxyethyl) adenine (Problem 4 - 18)
Naesens, Balzarini, and Clercq, "Pharmacokinetics in Mice of the Anti-Retrovirus Agent 9-(2-phophonylmethoxyethyl) adenine",
Drug Metabolism and Disposition (1992), p. 747- 752.
9-(2-phophonylmethoxyethyl) adenine (PEMA) is an anti-retrovirus (anti-HIV) agent. The pharmacokinetics of
PEMA in mice were established in a study by . In this study there were three different PEMA doses given: 25 mg/kg,
100 mg/kg, and 500 mg/kg. Each of these doses was injected intravenously into male mice. The data obtained from
study using the 25 mg/kg dose is summarized in the following table:
From the data presented in the preceding table, determine the following. (Assume that the mouse weighs 200g.)
1. Find the elimination rate constant, .
2. Find the half life, .
3. Find .
4. Find .
5. Find the Area Under the Curve, .
6. Find the area under the first moment curve, .
7. Find the volume of distribution,
8. Find the clearance, .
Problem Submitted By: Maya Lyte AHFS 12:34.56 Antivirals
Problem Reviewed By: Vicki Long GPI: 1234567890 Antivirals
PROBLEM TABLE 4 - 18. 9-(2-phophonylmethoxyethyl) adenine
Time (minutes)
Serum concentration
2.0 90.3
2.9 83.9
5.6 67.3
8.9 51.5
10.5 45.2
13.5 35.4
15.0 31.3
20.0 20.9
24.0 15.1
59.6 0.9
µg
mL
--------
k
t
½
MRT
C
p
( )
0
AUC
AUMC
V
d
Cl
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-44
(Problem 4 - 18) Pema:
1.
2. .
3. .
4. .
5. .
6. .
7.
8. .
0 10 20 30 40 50 60
Time (min)
10
-1
10
0
10
1
10
2
C
o
n

(
u
g
/
m
L
)

C
O
N
C
E
N
T
R
A
T
I
O
N

(
M
I
C
/
M
L
)
k 0.08min
1 –
=
t
½
8.67min =
MRT 12.5min =
C
p
( )
0
105
µg
mL
-------- =
AUC 1300
µg hr ⋅
mL
----------------- =
AUMC 16250
µg hr
2

mL
------------------- =
V
d
47.6ml =
Cl 3.8
mL
min
--------- =
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-45
Thioperamide (Problem 4 - 19)
Sakurai, et. al., "The Disposition of Thioperamide, a Histamine H3-Antagonist, in Rats", J. Pharm. Pharmacol. (1994), p. 209 -
212.
Thioperamide is a histamine (H3) receptor-antagonist. In a study by Sakurai et al, rats were given 10 mg/kg intrave-
nous injections of Thioperamide. The following data was obtained from the study:
From the data presented in the preceding table, determine the following:
1. Find the elimination rate constant, .
2. Find the half life, .
3. Find .
4. Find .
5. Find the Area Under the Curve, .
6. Find the area under the first moment curve, .
7. Find the volume of distribution,
8. Find the clearance, .
Problem Submitted By: Maya Lyte AHFS 12:34.56 Antivirals
Problem Reviewed By: Vicki Long GPI: 1234567890 Antivirals
PROBLEM TABLE 4 - 19. Thioperamide
Time (minutes)
Serum concentration
3.7 3.1
7.5 2.8
13 2.4
45 1.1
60 0.74
120 0.16
µg
mL
--------
k
t
½
MRT
C
p
( )
0
AUC
AUMC
V
d
Cl
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-46
(Problem 4 - 19) thioperamide:
1.
2. .
3. .
4. .
5. .
6. .
7.
8. .
0 20 40 60 80 100 120
Time (min)
10
-1
10
0
10
1
C
o
n

(
u
g
/
m
L
)

C
O
N
C
E
N
T
R
A
T
I
O
N

(
M
I
C
/
M
L
)
k 0.0254min
1 –
=
t
½
27.3min =
MRT 39.4min =
C
p
( )
0
3.39
µg
mL
-------- =
AUC 133.5
µg min ⋅
mL
--------------------- =
AUMC 5256
µg min
2

mL
----------------------- =
V
d
Dose
Cp
0
-------------
10
mg
kg
-------
3.39
µg
mL
--------
mg
1000µg
-------------------
1000mL
L
-------------------- ⋅ ⋅
-------------------------------------------------------------------- 2.95
L
kg
----- - = = =
Cl 0.0254min
1 –
2.95
L
kg
------
1000ml
L
------------------ 75
mL
min kg ⋅
-------------------- = ⋅ ⋅ =
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-47
Cocaine (Problem 4 - 20)
Khan,vM. et. al. “Determination of pharmacokinetics of cocaine in sheep by liquid chromatography” J. Pharm. Sci. 76:1 (39-43)
Jan 1987
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-48
4.1.3 URINE
From the Laplace Transform of a drug given by IV bolus we find that :
(EQ 4-10)
where Xu is the cumulative amount of drug in the urine at time t. Rearranging, we
get:
(EQ 4-11)
where the amount of drug that shows up in the urine at infinite time, .
Thus a plot of vs. time on semi-log paper would result in a straight line
with a slope of -K and an intercept of .. and we can get k
u
from the intercept
and the slope. Rearranging the intercept equation, we get This method
of obtaining pharmacokinetic parameters is known as the Amount Remaining to be
Excreted (ARE) method.
TABLE 4-4 Enalapril urinary excretion data from 5 mg IV Bolus
Time (hr)
Cumulative
Enalapril in urine
(mg)
mg
1 0.41 0.59
2 0.65 0.35
3 0.80 0.20
4 0.88 0.12
6 0.96 0.04
1.0 ------
X
u
k
u
K
----- X
0
1 e
K t ⋅ – ( )
– ( ) ⋅ ⋅ =
X
u
( )

X
u

k
u
K
-----
. ,
| `
X
0
e
Kt –
⋅ ⋅ =
X
u
( )

k
u
K
----- X
0
⋅ =
X
u
( )

X
u

X
u
( )

k
u
K =
X
u
( )

X
0
-------------- ⋅
X

u
X
u

I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-49
Utilizations: A.R.E.
Method
FIGURE 4-2. Cumulative Enalapril in urine
• You should be able to transform a data set containing amount of drug in the urine vs. time into
cumulative amount of drug in the urine vs. time and plot the ARE. (Amount Remaining to be
Excreted -> vs. time on semi-log yielding a straight line with a slope of
and an intercept of
• You should be able to determine the elimination rate constant, K1, from cumulative urinary
excretion data. (Calculate the slope of the graph on SL paper.)
• You should be able to determine the excretion rate constant, ku, from cumulation urinary excre-
tion data. (Divide the intercept of the graph by X
0
and multiply by K1.
)
• You should be able to determine .
• You should be able to calculate percent metabolized or excreted from a data set. Thus,
Percent metabolized = and percent excreted unchanged = assuming
A second method is to plot the rate at which the drug shows up in the urine over
time. Again, using the LaPlace transforms, we find that:
(EQ 4-12)
Utilization: Rate of
excretion method
Thus, a plot of the rate of excretion vs. time results in a straight line on semi-log
paper with a slope of -K1 and an intercept, R
0
, of k
u
X
0
. Rearranging the intercept
0 1 2 3 4 5 6
10
10
10

X
u
(
i
n
f
)

-

X
u
0
-1
-2
Hours
1.3 hr
half life
0.2
0.1
X
u
( )

X
u cum ( )
– { ¦
K 0.533 hr
1 –
– = – X
u
( )

k
u
X
0

K
--------------- 1.0 mg = =
k
u
K =
X
u
( )

X
0
-------------- 0.53 hr
1 – 1.0 mg
5.0 mg
----------------- 0.106 hr
1 –
= ⋅ = ⋅
k
m
K k
u
k
m
+ =
k
m
K
------ 100 ⋅
k
u
K
----- 100 ⋅
K k
u
k
m
+ =
dX
u
dt
--------- k
u
X
0
e
K t –
R
0
e
K t –
⋅ = ⋅ ⋅ =
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-50
equation yields . In real data, we don’t have the instantaneous excretion
rate , but the average excretion rate, , over a much larger interval. What
that means to our calculations is that over the interval of data collection, the total
amount of drug collected divided by the total time interval is the average rate. In
the beginning of the interval the rate was faster than at the end of the interval. So
the average rate must have occurred in the middle of the interval. Thus equation 4-
12 which is the instantaneous rate can be rewritten to
(EQ 4-13)
TABLE 4-5 Enalapril Urinary Rate Data
• You should be able to transform a data set containing amount of drug in the urine vs. time inter-
val into Average Rate, , vs. ,(t mid the time of the midpoint of the interval), on semilog
yielding a straight line with a slope of and an intercept of . as shown below.
• You should be able to determine extrapolate the line to . The value of Rate (at
), R
0
, = which when divided by .is k
r
.
Interval (hr) t(mid)
Enalapril in
urine ,(mg)
0-1 0.5 1 0.41 0.41
1-2 1.5 1 0.24 0.24
2-3 2.5 1 missed sample ?
3-4 3.5 1 0.08 0.08
4-6 5 2 0.08 0.04
k
u
R
0
X
0
------ =
t d
dX
u
∆X
u
∆t
----------
∆X
u
∆t
---------- k
u
X
0
e
K t
mid

R
0
e
K t
mid

⋅ = ⋅ ⋅ =
∆t
∆X
u
∆X
u
∆t
----------
∆X
u
∆t
---------- t
K – k
u
X
0

0 1 2 3 4 5
10
-2
10
-1
10

T (Mid)
U
r
i
n
a
r
y

E
x
c
r
e
t
i
o
n

R
a
t
e

(
m
g
/
h
r
)
-1
-2
0
1.3 hr
half life
R0 = 0.53 mg/hr
k
u
t 0 =
t 0 = k
r
X
0
0.53 mg hr ⁄ ( ) = ⋅ X
0
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-51
Thus,
• You should be able to determine .
• You should be able to calculate percent metabolized or excreted from a data set.
The rate equation is superior clinically because the ARE method requires collec-
tion of all of the urine which is usually only possible when you have a catheterized
patient while the Rate Method does not. (People don’t urinate on command, and
your data could be in the toilet, literally.)
An additional advantage of the rate equations is that the has the units of
mass, which gives the total amount of drug excreted into the urine directly. Thus:
AN INTERESTING OBSERVATION: If you look at the LaPlace Transform of the
rate equation for any terminal compartment, you would see that the resulting equa-
tion is that of the previous compartment times the rate constant through which the
drug entered the terminal compartment. Thus, the rate of drug showing up in the
urine (terminal compartment) is:
where k
u
is the rate constant through which the drug entered the urine and
is the equation of the previous compartment.
R
0
X
0
------
0.53mg/hr
5mg
------------------------- 0.106hr
1 –
= =
k
m
K k
u
k
m
+ =
AUC

0
AUC

0
R
0
K
------
0.53 mg/hr
0.53 hr
1 –
-------------------------- 1 mg = = =
dX
u
dt
--------- k
u
X
0
e
K t –
R
0
e
K t –
⋅ = ⋅ ⋅ =
dX
dt
------- X
0
e
K t –
⋅ =
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-52
4.2 Metabolite
4.2.1 PLASMA
Remember, the LaPlace Transform of the metabolite data yielded
or depending on
which rate constant that we arbitrarily assigned to be K, the summation of all the
ways that the drug is removed from the body and K1, the summation of all the
ways that the metabolite is removed from the body. When we begin to manipulate
the data, we know that we have a curve with two different exponents in it. (If they
were the same, the equation would be different.) We don’t know which is bigger,
K1 or K, but we can rewrite the equation to simply reflect K
large
and K
small
, know-
ing that one is K1 and the other is K but not which is which. If we, then, devided
both sides of the equation by Vdm, the volume of distribution of the metabolite,
we would get :
(EQ 4-14)
Utilization:
Curve Stripping
• You should be able to plot a data set of plasma concentration of metabolite vs. time on semi-log
paper yielding a bi-exponential curve.
as . And faster than . So, at some long
time, t, . In fact is small enough to be ignored. Thus at long
time, t, the equation becomes :
(EQ 4-15)
So that the plot of the terminal portion of the graph would yield a straight line with a slope of
-K
small
and an intercept of I =
• You should be able to obtain the slope of the terminal portion of the curve, the negative of
which would be the smaller of the two rate constants, , (either the summation of all the
ways that the drug is eliminated, , or the summation of all the ways that the metabolite is
eliminated, ).
• Subtracting the two previous equations yields
X
m
k
m
X ⋅
o
( )
K1 K – ( )
---------------------- e
K – t
e
K – 1t
– ( ) ⋅ = X
m
k
m
X ⋅
o
( )
K K1 – ( )
---------------------- e
K – 1t
e
Kt –
– ( ) ⋅ =
C
pm
k
m
K
l e arg
K
small

--------------------------------------
. ,

| `
X
0
V
dm
----------
. ,

| `
e
K
small
t ⋅ ( ) –
e –
K
l e arg
t ⋅ ( ) –
. ,

| `
=
e
Kt –
0 → t ∞ → e
k
l e arg
t –
0 → e
k
small
t –
0 →
e
K
l e arg
t –
e
K
small
t –
« e
K
l e arg
t –
C
pm
k
m
K
l e arg
K
small

-----------------------------------
. ,
| `
X
0
V
dm
---------
. ,
| `
e
K
small
t ⋅ ( ) –
. ,
| `
=
k
m
K
l e arg
K
small

-----------------------------------
. ,
| `
X
0
V
dm
---------
. ,
| `
K
small
K
K1
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-53
(EQ 4-16)
which is a straight line on semi-log paper with a slope of -k
big
and an intercept of
. Note: we can get the larger of the two rate constants from this
method.
TABLE 4-6
In the above data Cp vs. Time is the plasma profile of the drug from Table 4-1 on page 2 and
Cpm1 vs. Time is the plasma profile of the metabolite. A plot of Cp vs. Time yielded a straight
line with a slope,(-K) of -0.375 hr
-1
,

and

and intercept of 295 mic/
L,
Drug Metabolite
(1) (2) (3) (4) (5)
Time (hr)
Cp
(mcg/L) Cpm1 (mcg/L)
0 0 181.2 181.2
0.5 24.7 175 150.3
1 44.4 168.9 124.5
2 139 71.8 157.5 85.7
4 65.6 96.5 136.9 40.4
6 31.1 100 119 19
8 14.6 94.7
12 76.5
24 34
C
pm
C
pm

k
m
K
l e arg
K
small

-----------------------------------
. ,
| `
X
0
V
dm
---------
. ,
| `
e
K
big
t ⋅ ( ) –
. ,
| `
=
I
k
m
K
l e arg
K
small

------------------------------------
. ,
| `
=
X
0
V
dm
---------
. ,
| `
Cpm Cpm Cpm –
K
0.693
1.85 hr
1 –
---------------------- 0.375 hr
1 –
= =
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-54
Figure 4-1 on page 3 (column 2 vs. 1 in Table 4-6 on page 53)
while a plot of Cpm1 vs. Time( Figure 4-3 on page 54) yields a biexponential plot with a termi-
nal slope of 0.07 hr
-1
, and extrapolating the terminal line back to time = 0
yields 181 mic/L.
FIGURE 4-3. Nifedipine Metabolite (column 3 vs. 1 in Table 4-6 on page 53)

0 2 4 6 8
Time (hours)
10
1
10
2
10
3
C
o
n
c
e
n
t
r
a
t
i
o
n

(
n
g
/
m
L
)

Cpo = 295 mic/L
C
o
n
c
e
n
t
r
a
t
i
o
n

(
m
i
c
/
L
)
Time (hr)
50
100
1.85 hr
k
small
0.693
10 hr
------------- =
Nifedipine IV bolus - Metabolite
Time (hours)
)

0 4 8 12 16 20 24
10
1
10
2
10
3
C
o
n
c
e
n
t
r
a
t
i
o
n

(
m
i
c
/
L
)
10 hr
80
40
Cpm0 181
mic
L
--------- =
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-55
• You should be able to feather (curve strip) the other rate constant out of the data by plotting the
difference between the extrapolated (to ) terminal line (column 4 vs. 1 in Table 4-6 on
page 53) and the observed data (at early times) (column 3 vs. 1 in Table 4-6 on page 53) yield-
ing a straight line with the slope of the line equal to the negative of the other (larger) rate con-
stant (column 5 vs. 1 in Table 4-6 on page 53).
First you would fill in the column (column 4 in Table 4-6 on page 53) by computing
for various values of time i.e where is the terminal slope of the
graph. Then (column 5 in Table 4-6 on page 53) would be column 4 - column 3.
Then a plot of vs. time (column 5 vs. 1 in Table 4-6 on page 53) is shown below.
FIGURE 4-4. Curve strip of Nifedipine Metabolite data
In this case, the slope of the stripped line line is -0.375 hr
-1
and the intercept is 0.181.2 mic/L.
The slope of -0.375 hr
-1
should not be surprising as the plot of the data in Figure 4-3 on page 54
resulted in a terminal slope of -.07 hr
-1
. Since the data set yielded a bi-exponential plot, sepa-
rating out the exponents could only yield K (0.375 hr
-1
) or K1 as determined by our Laplace
Transform information. Thus, the terminal slope could be either -K1 or -K. Since it was obvi-
ously not -K, it had to be -K1. Thus the other rate constant obtained by stripping has to be K.
You can determine which slope is which rate constant if you have any data regarding intact drug
(i e. either plasma or urine time profiles of intact drug) as the slope of any of those profiles is
always .
• You should be able to determine if you have any urine data regarding intact drug (i.e.
urine time profiles of intact drug) as the intercept of those profiles allow for the solution of .
Thus the intercept, I, of the extrapolated line of equation 4-14 could be rearranged to contain
only one unknown variable, .
t 0 =
Cpm Cpm
Cpm Cpm0 e
k
small
t –
⋅ = k
small

Cpm Cpm –
Cpm Cpm –
0 1 2 3 4 5 6
10
1
10
2
10

Time (hr)
1
2
3
C
o
l
u
m
n

5
1.85 hr
Intercept
100
50
Half life
K –
V
dm
k
m
V
dm
k
m
X
0

K
l e arg
K
small
– ( ) I ⋅
-----------------------------------------------
0.375hr
1 –
25mg
1000 mic
mg
---------------------- ⋅ ⋅
0.375 0.07 – ( ) hr
1 –
181.2
mic
L
--------- ⋅
-------------------------------------------------------------------------- 170 L = = =
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-56
Utilization:
MRT Calculations
• You should be able to determine the rate constants using MRT calculations.
In a caternary chain, each compartment contributes its MRT to the overall MRT of the drug,
thus:
Flow Chart 4-4 IV Bolus
Suppose the drug were given by IV bolus. Then the drug would have to be metabolized and the
metabolite eliminated. Since the MRTs are additive, the overall MRT of the metabolite would
be made up of the MRTs of the two processes, thus:
Flow Chart 4-5 Metabolite
Thus, using the data from Table 4-3 on page 5 the MRT
(IV)Trap
is
hr or about hr using calculus.
And using the data from columns 1 and 3 from Table 4-6 on page 53 the MRT(met) using calcu-
lus is hr.
MRT
(elim)
= MRT
(met)
- MRT
(IV)
= 17 hr - 2.67 hr = 14.33 hr = 1/K2. Thus K2 = 0.07 hr
-1
.
X
K
MRT(IV) = 1/K
kmu km
Xm X
MRT(met) = MRT(elim)+MRT(IV)
MRT(met) = 1/K1 + 1/K
MRT
AUMC
AUC
------------------ =
1986.1
819.9
---------------- 2.42 = = MRT
AUMC
AUC
------------------ =
2100
787
------------ 2.67 = =
MRT
AUMC
AUC
------------------ =
36000
2116
--------------- 17 = =
I.V. Bolus Dosing
Basic Pharmacokinetics REV. 00.1.27 4-57
4.2.2 URINE
Valid equations:
(EQ 4-17)
Utilization: as in the previous urinary rate equation, clinically we work with the average rate
over a definite interval which results in rewriting equation 4-17 as:
(EQ 4-18)
• You should be able to plot a data set of rate of metabolite excreted vs. time (mid) on semi-log
paper yielding a bi-exponential curve.
• You should be able to obtain the slope of the terminal portion of the curve, the negative of
which would be the smaller of the two rate constants (either or ).
• You should be able to feather (curve strip) the other rate constant out of the data by plotting the
difference between the extrapolated (to ) terminal line and the observed data (at early
times) yielding a straight line with the slope of the line equal to the negative of the other (larger)
rate constant (either or ).
• You should be able to utilize MRT calculations to obtain and .
• You should be able to determine which slope is which rate constant if you have any data regard-
ing intact drug (i.e. either plasma or urine time profiles of intact drug) as the slope of any of
those profiles is always .
By this time, it should be apparent that data which fits the same shape curve
(mono-exponential, bi-exponential, etc.) are treated the same way. When the
curves are evaluated, the slopes and intercepts are obtained in the same manner.
The only difference is what those slopes and intercepts represent. These represen-
tations come from the equations which come from the LaPlace Transforms which
come from our picture of the pharmacokinetic description of the drug. Please
refer back to the section on graphical analysis in the Chapter 1, Math review for a
interpretation of slopes and intercepts of the various graphs.
Temporarily, please refer to exam section 1, chapter 14 for problems for this sec-
tion (until problems can be generated) as well as additional problems for the previ-
ous sections.
dX
mu
dt
-------------
k
mu
k
m
X
0

K
l e arg
K
small
– ( )
---------------------------------------- e
K
small
t –
e
K
l e arg
t –

¹ ¹
' '
¹ ¹
⋅ =
∆X
mu
∆t
-------------
k
mu
k
m
X
0

K
l e arg
K
small
– ( )
---------------------------------------- e
K
small
t
mid

e
K
l e arg
t
mid

¹ ¹
' '
¹ ¹
⋅ =
K1 K
t 0 =
K1 K
K1 K
K –