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PHARMACOKINETICS
 Introduction
Definitions:
•Pharmacokinetics
The kinetic study of ADME (Absorption,
Distribution, Metabolism and Elimination) of
the drug.

• Clinical pharmacokinetics
The application of pharmacokinetic data
to the most effective and safe therapeutic
management of the individual patient.
Drug Absorption

The process of uptake of the

compound from the site of
administration into the systemic
circulation (the appearance of the drug in
the blood).
Drug plasma level-time curve;
After a single oral dose of a drug, a typical plasma drug
concentration time curve is obtained.

C max

Absorption phase Ka

MSC

Therapeutic range
MEC
Elimination phase

t max
a. Pharmacokinetic parameters;

1. Peak plasma concentration ‘C max’ :

The maximum plasma concentration,
related to the dose, rate of absorption (ka),
rate of elimination (k).

2 . Time of peak concentration ‘t max’ :

The time to C max.

3 . Area under the curve ‘AUC’ :

This equal to the total amount of drug
absorbed after administration.
 b. Pharmacodynamic parameters;

1. Minimum effective concentration ‘MEC’ :

The minimum concentration of drug in
plasma required to produce the desired
therapeutic effect. The concentration below
MEC is regarded the sub- therapeutic
concentration.

2. Maximum safe concentration ‘MSC’ :

It is also known as the minimum toxic
concentration, the concentration of a drug in
plasma beyond which side effects will
results. Concentration above the MSC is
regarded to be in the toxic level.
3. Therapeutic range or therapeutic window :
The range of plasma concentration between
MEC and MSC, As long as the drug level is
maintained within the therapeutic window,
the therapeutic effect of the drug is
observed without side effect.

Onset of action:
The beginning of pharmacological response,
it takes places when the plasma
concentration just exceeds the required
MEC.
Duration of action:
The period of time for which the
plasma concentration of the drug
remain above the MEC level.

Fraction of drug absorbed ‘F’ :

The ratio of the amount of drug
ultimately reaching the plasma
stream to the total dose
administered. The value of
dosage forms often show F values less than the
unity because of the under mention factors;

1. Slow release of drug from the dosage form and

loss of the unabsorbed drug through faces.

2. Degradation of the drug in the GIT due to

chemical or enzymatic processes.

3. Drugs undergo the first pass metabolism, they

may be stable in the GIT and completely
absorbed but extensively metabolized in the
liver before reaching the blood.
 Kinetics:
The study dealing with
the rate of chemical and physical
reactions
And
the factors which influence the
reaction rate.
 Rates:

Is the velocity within which the reaction

occurs.

Consider the following reaction:

Drug A drug B

The amount of drug A is decreasing with respect to time

So, Rate = - dA / dt (forward reaction)

Or
the amount of B increases with respect to time
Rate = + dB / dt
The order of a reaction:
Refers to the actual manner in which
the concentration of the drug tends to
influence the rate of reaction or process.
 Zero order kinetics (constant rate
process):
Constant rate change and the change
independent on the concentration.

It is not possible to increase the rate of

process by increasing the concentration of
the drug
 Time Amount remaining (mg)
(hours)
0 100
1 80
2 60
3 40
4 20

The amount of the drug A is decreasing at a constant time interval t

A = Ao - ko t

Where, Ao = the amount of the drug at time = zero

A = the amount of the drug at time = t
 A plot of A versus time yield a straight line
having a slope = - K and intercept = Ao

A = Ao - ko t

120 0.8

100
Constant drug
Constant drug lossloss
80 Slope = - k
A mg

dA/dt
60

40

20

0
0.7
0 1 2 3 4 5
0 1 2 3 4 5
Tim e hrs
Tim e hrs
 The half-life (t ½);
Expresses the period of time required
for the amount or concentration of a drug
to decrease by one half,

• t ½ for zero order reaction :

t ½ = Ao / 2 ko

E.g., for zero order delivery:

1. Sustained release
2. I.V infusion
3. Trans-dermal preparations
First order kinetics (linear kinetics):

The rate of reaction is directly proportional to the concentration.

i.e., the change depends on the concentration.
E.g.

Time Amount remaining

0 100
1 60
2 30
3 20
 ln A = ln Ao - k t

•Since ln = 2.303 log,

Log A = log Ao – k t / 2.303

• t ½ for first order reaction:

t ½ =0.693/ k
•A plot of log A versus time;
a straight line is obtained whose slope = -k / 2.303 and
intercept = log Ao

2.5
y = -0.24x + 1.995
2
2 R = 0.99

1.5
log A

0.5

0
0 1 2 3 4
Time hrs
 Pharmacokinetic Model:
Is a mathematical model devised to simulate the rate process of
drug absorption, distribution and elimination. These mathematical
models make possible the development of equations to describe
drug concentration in the body as a function of time.

N.B. There are three different approaches to pharmacokinetic

analysis of experimental data;

1. Compartment modeling
2. Non-compartment modeling
3. Physiological modeling
Compartment modeling:

Is the most common approach to pharmacokinetic

characterization of a drug.

Compartment:

Is a tissue or a group of tissues that have similar blood flow or

drug affinity.

NOTES;
A compartment is not real physiological or anatomic region.
The rate constants are used to describe drug movement in and out
of the compartments.
The nature and behavior of the drug determines the number of the
compartments
E.g., some drugs go to 2 places so we have two compartments
The model is open system because drug can be eliminated from
the system
 Compartment models;
Model 1: One compartment open model, IV injection;

1 K

Model 2: One compartment open model with first order

absorption;

Ka 1
K

Model 3: two compartment open model, IV injection;

k12
1 2
k21
k
Model 4: two compartment open model with first order
absorption;

k12
Ka 1 2
k21
k

• N.B.
• k = Pharmacokinetic rate constant
• Compartment 1 = represent the plasma or the central
compartment
• Compartment 2 = represent the tissue compartment.
 The drawing of models has 3 functions:

1. Enables the pharmacokinetic to write differential equations to describe

drug concentration change in each compartment.
2. Give visual representation of rate process
3. Show how many pharmacokinetic constants are necessary to describe the
process adequately.

Uses of pharmacokinetic model;

1. Predict plasma, urine and tissue drug levels with any dosage regimen
2. Calculate the optimum dosage regimen for each patient individually
3. Estimate the possible accumulation of drugs and/or metabolites
4. Correlate drug concentration with pharmacologic or toxicological activity
5. Evaluate differences in the rate or extent of bioavailability between
formulations
6. Describe how changes in physiology or disease affect the absorption,
distribution, or elimination of the drug
7. Explain drug interaction
8. Give a good picture concerning protein binding
Physiologic Compartment