EXPERIMENT NO.

CALCULATION OF VARIOUS PHARMACOKINETIC PARAMETERS AFTER IV BOLUS INJECTION-I

Aim

To calculate various pharmacokinetic parameters from given blood data of IV bolus injection (one
compartment model).
Learning objective
To understand calculation of various pharmacokinetic parameters after one compartment IV bolus
administration following first order elimination.
Requirements
Regular graph paper, semilog graph paper, calculator and pencil.

Given data
Plasma data obtained after a bolus dose of 184 mg of ceftriaxone, a semi synthetic cephalosporin antibiotic, in a
newborn infant is summarized below:

Time 1 6 12 2 4 7 9 14
(h) 4 8 2 6 4
Conc 13 12 10 7 4 2 1 3.7
7 0 3 6 2 3 2
(mg/l)
1. Prepare a semilogarithmic plot and estimate the half-life of drug
2. Estimate the total AUC
3. Calculate volume of distribution
4. Calculate total clearance.
Solution
Note: If the graph of concentration versus time is plotted on regular graph paper, the curvilinear plot is obtained
which makes it difficult to calculate slope and hence the semilog plot is used which gives the linearity and makes
it easy and accurate to calculate the pharmacokinetic parameters (Refer figure 1).
1. Semilog Plot
a. Plot the graph on semi logarithmic graph paper as the elimination data follows first order kinetics.
b. According to the given data select number of cycles on semilog paper.
c. Plot concentration on Yaxis and time on X axis.
d. Mark concentration for respective time on the graph paper.
e. Draw a straight line in such a way that it covers maximum elimination phase points up to Yaxis.
f. Yintercept is the C0 concentration
g. Determine slope of the line and calculate elimination rate constant.

2. Elimination half life

 entration as (C, 20). From that point draw a straight line which intersects plotted line (refer figure 2).
This point would be the first point of intersection From intersected point draw perpendicular straight line
on X axis which gives the time (t1).
b. On Y axis draw a second straight line from half concentration of initial (C/2, 10) which intersects plotted
line. This will be the second point of intersection. From that point draw perpendicular on X axis which
gives the time (t2).
c. Calculate half life by subtracting t2 form t1.

Figure 1. Regular and semilog plot of plasma concentrations versus time showing y intercept and
slope

Figure 2. Semilog plot of plasma concentration versus time showing determination of half life

1. Elimination rate constant

Calculate elimination rate constant by using slope of line.

Slope= logC2-log C1 / t2 – t1

K = -(slope x 2.303)

2. Elimination half life

Calculate elimination half life by using following formula
t1/2 = 0.693/K
Alternatively, half life can be determined graphically

3. Area Under Curve (AUC)

By using concentration at zero time AUC can be calculated from following
equation (Y intercept is C0 concentration).
 ng following equation
Cl= KV

Applications
1. Various pharmacokinetic parameters can be estimated.
2. Pharmacokinetic parameters are very useful in calculating the dose of new drug.
3. Bioequivalence study can be undertaken based on plasma data of various brands.

Result
The various pharmacokinetic parameters calculated from given plasma
data of ceftriaxone are given in table below:

Sr. No. Parameter Result

1 Biological half
life
2 Elimination rate
constant
3 Total AUC

4 Volume of
Distribution
5 Clearance

EXPERIMENT NO.2

CALCULATION OF VARIOUS PHARMACOKINETIC PARAMETERS AFTER IV BOLUS INJECTION-II

Aim

To calculate various pharmacokinetic parameters from given blood data of IV bolus injection (one
compartment model).
Learning objective
To understand calculation of various pharmacokinetic parameters after one compartment IV bolus
administration following first order elimination.
Requirements
Regular graph paper, semilog graph paper, calculator and pencil.

Given data
 mg phenylethylmalonide (PEMA), a metabolite of antiepileptic drug primidone is F
summarized in table below. i
g
0.3 0.5 0.6 1.5 2 4 6 10 16 24 32 48 u
Time r
3 7
(h) e
Conc 14. 12.6 11 9 8. 7. 6.6 6.2 4. 3. 2.3 1.2
(mg/l)
7 2 9 6 2 1
.
a. Prepare a semilogarithmic plot and estimate the half-life of drug
b. Estimate the total AUC R
c. Calculate volume of distribution e
d. Calculate total clearance. g
Solution u
l
Note: If the graph of concentration versus time is plotted on regular graph paper, the curvilinear plot is obtained a
which makes it difficult to calculate slope and hence the semilog plot is used which gives the linearity and makes r
it easy and accurate to calculate the pharmacokinetic parameters (Refer figure 1).
a
1. Semilog Plot
n
a. Plot the graph on semi logarithmic graph paper as the elimination data follows first order kinetics. d
b. According to the given data select number of cycles on semilog paper.
s
c. Plot concentration on Yaxis and time on X axis. e
m
d. Mark concentration for respective time on the graph paper.
i
e. Draw a straight line in such a way that it covers maximum elimination phase points up to Yaxis. l
h. Yintercept is the C0 concentration o
g
i. Determine slope of the line and calculate elimination rate constant.
p
l
3. Elimination half life o
d. On Y axis near to elimination phase select initial concentration as (C, 20). From that point draw a straight t
line which intersects plotted line (refer figure 2). This point would be the first point of intersection From
intersected point draw perpendicular straight line on X axis which gives the time (t1). o
f
e. On Y axis draw a second straight line from half concentration of initial (C/2, 10) which intersects plotted
line. This will be the second point of intersection. From that point draw perpendicular on X axis which p
gives the time (t2). l
f. Calculate half life by subtracting t2 form t1. a
s
m
a

c
o
n
c
e
n
t
r
a
t
ions versus time showing y intercept and
slope Sr. No. Parameter Result
1 Biological half
life
Figure 2. Semilog
plot of plasma 2 Elimination rate
constant
concentration
3 Total AUC
versus time
showing 4 Volume of
determination of Distribution
half life 5 Clearance EXPERI
MENT
5. Elimination rate constant
NO. 3
Calculate elimination rate constant by using slope of line.

Slope= logC2-log C1 / t2 – t1
CALCUL
ATION
K = -(slope x 2.303)
OF
VARIOU
6. Elimination half life
S
Calculate elimination half life by using following formula
PHARM
t1/2 = 0.693/K ACOKIN
Alternatively, half life can be determined graphically ETIC
PARAM
7. Area Under Curve (AUC) ETERS
By using concentration at zero time AUC can be calculated from following AFTER
equation (Y intercept is C0 concentration). IV
AUC = C0 / K INFUSIO
8. Clearance N-III
Calculate clearance by using following equation
Aim
Cl= KV

Applications
4. Various pharmacokinetic parameters can be estimated.
5. Pharmacokinetic parameters are very useful in calculating the dose of new drug.
6. Bioequivalence study can be undertaken based on plasma data of various brands.

Result
The various pharmacokinetic parameters calculated from given plasma
data of ceftriaxone are given in table below:
 ous pharmacokinetic parameters from the given blood data of IV infusion (one
compartment model).
Learning objective
To understand calculations of various pharmacokinetic parameters after
one compartment IV infusion following first order elimination.
Prerequisite
Knowledge of pharmacokinetics of IV infusion.

Semilog plot of post infusion data

Requirements 10

Regular graph paper, semilog graph paper, calculator, pencil.

Given data 1

Estimate the volume of distribution, elimination rate constant, half life and
clearance from the data in following table obtained on infusing a drug at the rate of
0.1
50 mg/hr for 7.5 h. 0 5 10 15 20

Time 0 2 4 6 7. 9 12 15 Time (h)

5
(h)
Conc 0 3. 5. 6.5 7 4. 2 0.9 F
(mg/l) i
4 4 6
g
a. Prepare a semilogarithmic plot and estimate the half-life of drug
u
b. Calculate elimination rate constant r
c. Calculate volume of distribution e
Calculate total clearance
1
Solution Note: If the graph
.
linearity and makes it easy and accurate to calculate the pharmacokinetic
parameters (Refer figure 1). R
e
1. Semilog plot
g
a. Plot the graph on semi logarithmic graph paper as the elimination data follows first order u
kinetics. l
b. According to the given data select number of cycles on semilog paper. a
c. Plot concentration on Yaxis and time on X axis. r
d. Mark concentration for respective time on the graph paper.
a
e. Draw a straight line in such a way that it covers maximum elimination phase points. n
f. Determine slope of the line and calculate elimination rate constant. d
2. Elimination half life
a. On Y axis near to elimination phase select initial concentration (C1) and from that s
point, draw a e
m
straight line which intersects plotted line. This point would be the first point of i
intersection. From intersected point, draw perpendicular straight line on X axis l
which gives the time (t1). o
b. On Y axis draw a second straight line from half concentration of initial (C2) g
which intersects plotted line. This will be the second point of intersection. From p
that point draw perpendicular on X axis which gives the time (t2). l
c. Calculate half life by subtracting t2 form t1. o
t
 1. Elimination rate constant
Calculate elimination rate constant by using slope of line.

Slope= logC2-log C1 / t2 – t1

K = -(slope x 2.303)

2. Elimination half life

Calculate elimination half life by using following formula
t1/2 = 0.693/K
Alternatively, half life can be determined graphically
3. Volume of distribution
Calculate volume of distribution by using following equation
V = R0 / Kss

Where, R0 = infusion rate = 50 mg/h, Css = 7 mg/l.

· Consider concentration of drug in plasma compartment at the time of
stopping of infusion as Css (here Css = concentration at 7.5 h, as infusion was
EXPERI
stopped at 7.5 h). MENT
4. Clearance NO. 4
Calculate clearance by using following equation
Cl  KV
CALCUL
Also it can be calculated by using following formula ATION
OF
VARIOU
Cl = R0 / Css
S
Applications PHARM
1. Pharmacokinetic parameters during and after IV infusion can be estimated. ACOKIN
2. Steady state concentration of drug can be estimated. ETIC
Results PARAM
The various pharmacokinetic parameters calculated from given plasma data of ETERS
drug are given as
AFTER
follows: Sr. No. Parameter Result IV
1 Biological half life INFUSIO
2 Elimination rate constant N-IV
3 Volume of Distribution
4 Clearance
Aim
 culate various pharmacokinetic parameters from the given blood data of IV
infusion (one compartment model).
Learning objective
To understand calculations of various pharmacokinetic parameters after
one compartment IV infusion following first order elimination.
Prerequisite
Knowledge of pharmacokinetics of IV infusion.

Requirements
8
Regular graph paper, semilog
Regular graph
plot paper, calculator, pencil.
Semilog plot of post infusion data
7 10

Given data
6
1. Estimate the pharmacokinetic parameters from the data given in following
1
table obtained5on infusing droperidol at the rate of 0.125 mg/hr for 7.5 h.

Time4 0 0.5 2 4 6 8 10 14 0.1

18 24 26 28 30
0 5 10 15 20
(h) 3 0 5 10 15 20

Conc 0 0.9Time (h)

1.8 2.6 2. 2. 2.7 2. 2.9 3.1 Time
1.4(h) 0.6 0.3
2
(mg/l)
5 5 7 0 7 6
1
d. Prepare a semilogarithmic plot and estimate the half-life of drug
0
e. Calculate elimination rate constant
f. Calculate volume of distribution
Calculate total clearance

Solution Note: If the graph

linearity and makes it easy and accurate to calculate the pharmacokinetic
parameters (Refer figure 1).
3. Semilog plot
a. Plot the graph on semi logarithmic graph paper as the elimination data follows first order
kinetics.
b. According to the given data select number of cycles on semilog paper.
g. Plot concentration on Yaxis and time on X axis.
h. Mark concentration for respective time on the graph paper.
i. Draw a straight line in such a way that it covers maximum elimination phase points.
j. Determine slope of the line and calculate elimination rate constant.
4. Elimination half life
a. On Y axis near to elimination phase select initial concentration (C1) and from that
point, draw a
straight line which intersects plotted line. This point would be the first point of
intersection. From intersected point, draw perpendicular straight line on X axis
which gives the time (t1).
b. On Y axis draw a second straight line from half concentration of initial (C2)
which intersects plotted line. This will be the second point of intersection. From
that point draw perpendicular on X axis which gives the time (t2).
c. Calculate half life by subtracting t2 form t1.
 Figure 1. Regular and semilog plot
5. Elimination rate constant
Calculate elimination rate constant by using slope of line.

Slope= logC2-log C1 / t2 – t1

K = -(slope x 2.303)

6. Elimination half life

Calculate elimination half life by using following formula
t1/2 = 0.693/K
Alternatively, half life can be determined graphically
7. Volume of distribution
Calculate volume of distribution by using following equation
V = R0 / Kss

Where, R0 = infusion rate = 50 mg/h, Css = 7 mg/l.

· Consider concentration of drug in plasma compartment at the time of
stopping of infusion as Css (here Css = concentration at 7.5 h, as infusion was
stopped at 7.5 h).
8. Clearance
Calculate clearance by using following equation
Cl  KV

Also it can be calculated by using following formula

Cl = R0 / Css
Applications
3. Pharmacokinetic parameters during and after IV infusion can be estimated.
4. Steady state concentration of drug can be estimated.
Results
The various pharmacokinetic parameters calculated from given plasma data of
drug are given as
follows: Sr. No. Parameter Result
1 Biological half life
2 Elimination rate constant
3 Volume of Distribution
4 Clearance
 EXPERIMENT- 6

CALCULATION OF VARIOUS PHARMACOKINETIC PARAMETERS AFTER EXTRAVASCULAR ADMINISTRATION-VI

Aim: To calculate various pharmacokinetic parameters after extravascular administration

of drug (one compartment model).
Theory:
Administration of drug dose by an extravascular route involves passage of the drug by
absorption through a biological membrane. The plasma profile obtained following
extravascular administration of a drug is different from plasma profile of same drug

Absorption phase

Elimination phase

Time (h)

obtained after the drug administered as a rapid intravenous bolus injection because the
entire dose of administered drug is not absorbed all at once.

For a drug that enters the body by a first order absorption process, gets
distributed in the body according to one-compartment kinetics and is eliminated by a
first order process, the model can be depicted as follows

After extravascular administration, the rate of change in the amount of

drug in the body dA/dt is the difference between the rate of input (absorption),
dAa/dt and rate of output (elimination), dAe/dt.
Amount of drug in the body = Rate of absorption - Rate of elimination
The differential equation that follows relates changes in drug concentration in the
blood with time to the absorption and the elimination rates
…4

FAoKa
Intercept=
V (K-a K)

-K

Slope=
2.303

where dA/dt = rate of change of amount of drug in the blood; A= amount

of drug in the blood at time t; Aa = amount of absorbable drug at the absorption
site at time t; Ka = absorption rate constant; K elimination rate constant,
respectively, KaAa = first order rate of absorption and KA= first-order rate of
elimination.
Integration of equation 2 yields

…3

Where A = amount of drug in the body at time t; A0 = amount of drug at

the site of administration at t=0 (the administered dose), F = fraction of drug
absorbed.
Equation 3 shows that the amount of drug in the body or blood follows a
biexponential profile, first rising and then declining. For orally or extravascularly
administered drugs, generally Ka>>K; therefore, the rising portion of the graph
denotes the absorption phase. If K>>Ka (perhaps indicating a dissolution rate-
limited absorption) the exact opposite will hold true.
 Converting equation 3 into concentration form, as V=A/C

…4

Determination of elimination rate constant (K)

This parameter can be estimated from elimination phase of the plasma level time curve profile.
For most drugs administered extravascularly, absorption rate is significantly greater than the
elimination
a
rate i.e. K t>>Kt. Hence, one can say that e-Kat approaches to zero much faster
than does e-Kt . At this stage, when absorption is complete, the change in plasma
concentration is dependent only on elimination rate and equation 4
becomes

Aplot of C versus t yields a straight line with slope K/2.303.

Elimination half life

One can estimate elimination half life form elimination rate constant

Apparent volume of distribution

For a drug administered by oral, or any other extravascular route of administration, the
apparent volume of distribution cannot be calculated from plasma drug concentration data
alone. The reason is that the value of F (the fraction of administered dose that reaches the
general circulation) is not known. From equation 6 we get,

In the absence of data for the fraction of administered dose that reaches the general circulation,
the best one can do is to obtain the ratio of V/F:
Time of maximum drug concentration, peak time (tmax)
The peak time (tmax) is the time at which the body displays the maximum plasma
concentration, (Cmax). It occurs when the rate of absorption is equal to the rate of elimination.
At the peak time, therefore, KaAa = KA. The rate of change in plasma drug concentration
dc/dt = zero. This rate can be obtained by differentiating following equation 4.

Equation 11 indicates that peak time depends on, or is influenced by, only the absorption and
elimination rate constants; therefore, any factor that influences the absorption and the
elimination rate constants will influence the peak time value; however, the peak time is always
independent of the administered dose of a drug.

Maximum (peak) plasma concentration (Cmax)

There are three methods available for determining peak plasma concentration Cmax. Two are
given here: Method 1. Peak plasma concentration obtained from the graph of plasma
concentration versus time.
Method 2. Peak plasma concentration can also be obtained by using an equation 4,
 This parameter can be estimated from elimination phase of the
plasma level time curve profile. For most drugs administered
a extravascularly, absorption rate is significantly greater than the elimination
rate i.e. K t>>Kt. Hence, one can say that e-Kat approaches to zero
much faster than does e-Kt . At this stage, when absorption is complete,
the change in plasma concentration is dependent only on elimination rate and
equation 4
becomes

Transforming into log form, the equation 5 becomes:

Aplot of C versus t yields a straight line with slope K/2.303.

Elimination half life

One can estimate elimination half life form elimination rate constant

Apparent volume of distribution

For a drug administered by oral, or any other extravascular route of
administration, the apparent volume of distribution cannot be calculated
from plasma drug concentration data alone. The reason is that the value of F
(the fraction of administered dose that reaches the general circulation) is not
known. From equation 6 we get,
 In the absence of data for the fraction of administered dose that
reaches the general circulation, the best one can do is to obtain the ratio of
V/F:

Time of maximum drug concentration, peak time (tmax)

The peak time (tmax) is the time at which the body displays the
maximum plasma concentration, (Cmax). It occurs when the rate of
absorption is equal to the rate of elimination. At the peak time, therefore,
KaAa = KA. The rate of change in plasma drug concentration dc/dt = zero.
This rate can be obtained by differentiating following equation 4.

Equation 11 indicates that peak time depends on, or is influenced

by, only the absorption and elimination rate constants; therefore, any factor
that influences the absorption and the elimination rate constants will
influence the peak time value; however, the peak time is always
independent of the administered dose of a drug.
Maximum (peak) plasma concentration (Cmax)
There are three methods available for determining peak plasma
concentration Cmax. Two are given here: Method 1. Peak plasma
concentration obtained from the graph of plasma concentration
 versus time.
Method 2. Peak plasma concentration can also be obtained by using an equation 4,

Obtain intercept by plotting plasma concentration versus time profile on semilog paper.
Given Data
After an oral administration of 500 mg drug, the following data was obtained

Time (h) 0.5 1 1.5 2 4 6 10 16 24 32 48

Plama Conc (mg/l) 2.4 3.8 4.2 4.6 8.1 5.8 5.1 4.1 3.0 2.3 1.3

1. Determine elimination rate constant and elimination half life.

2. Determine total AUC.
3. Determine Cmax and Tmax.

SOLUTION:
Table 1. Determination of AUC

Time C
Segme Cn1  tn-tn-1 AUC
h g/m Cn
l nt
2
0.25 51.33 A
0.5 74.05 B
0.75 82.91 C
 1 85.11 D
1.5 81.76 E
2 75.51 F
3 62.98 G
4 52.32 H
6 36.08 I
8 24.88 J
12 11.83 K
18 3.88 L
24 1.27 M
AUC0-
24
Clast/
K
Total AUC= AUC 0-24 + Clast/K

Table 2. Determination of residual concentrations

Time Conentr Extrapolat Residual

h ation ed Conc.
(g/ml) C Cr  C  C
0.25 51.33
0.5 74.05
0.75 82.91
1 85.11
1.5 81.76
2 75.51
3 62.98
4 52.32
6 36.08
8 24.88
12 11.83
18 3.88
24 1.27
Calculations

1. Elimination rate constant and elimination half life

Plot a graph of decline in plasma concentration versus time on semilog paper and
determine slope of line.

K  ( Slope  2.303)

2. Area under curve

Plot a graph of plasma concentration versus corresponding time on
simple graph paper and prepare segments Ato M.
3. Absorption rate constant (Ka)
Calculate absorption rate constant by using slope of line

4. Absorption half life

Calculate absorption half life by using following formula

5. Determination of tmax and Cmax

Conclusion
It can be concluded that various pharmacokinetic parameters can be
calculated after extravascular administration of drug.

Applications
 1.Various pharmacokinetic parameters can be estimated from given plasma data after
extravascular administration of drug.
2.Bioequivalence testing between various brands can be done. 3.Bioavailability of drug can
be studied.

Results
The various pharmacokinetic parameters calculated from given
plasma data of phenylpropanolamine hydrochloride are given as
follows:
Sr. No. Parameter Result
1 Elimination half life
2 Elimination rate constant
3 Cmax
4 tmax
5 Total AUC
6 Absorption rate constant
7 Absorption half life