د.نهله

Pharmacokinetics

Pharmacokinetics means what the body does to the drug or how the body deals with the drug or the fate of the drug in the body.
pharmacodynamics mean what a drug does to the body.
Pharmacokinetics includes the processes of Absorption, Distribution, Metabolism and Excretion.
Absorption is the process of a substance entering the body or the process take place before the drug appears in the circulation after administration at an extra vascular site.
Distribution is the dissemination of substances throughout the fluids and tissues of the body.
Metabolism is the irreversible biotransformation of substances and its daughter metabolites.
Excretion is the elimination of the substances from the body, may be by renal and biliary excretion of the drug molecule
Pharmacokinetics is sometimes abbreviated as PK.
Pharmacokinetics use words, symbols and mathematical equations which describe processes of pharmacokinetics and show the relationships between one variable and another.
Body compartment model:
To simplify the study of the pharmacokinetics of a drug, the body is represented as a system of compartments which have no physiological or anatomical existence.
The one compartment model:
Considers the body as a single homogenous compartment (central compartment .The drug enters the blood and rapidly distributed between blood and other body fluids and tissues.

The two compartment models system:

This model considers the body as it is consists of 2 compartments: a smaller central one and a larger peripheral one, between which drug exchanges occurs. The central compartment is often equated with the blood, but in fact it includes all those tissues and organs with which the drug is in rapid equilibrium (heart, kidney, liver, lungs) while the peripheral one (skin, muscles and fat)






Drug distributes to peripheral compartments in a reversible manner ( ) .
Drug is removed irreversibly ( ) from the central compartment, that is, it is excreted or metabolized.
To study the mathematical equations which describe the processes (absorption, distribution, excretion) we must start with the simplest example. If we give someone a rapid intravenous injection (termed a bolus) of a drug we introduce the drug directly into the blood and therefore we are study only the distribution and elimination. If the drug we have administrated is very rapidly distributed, we are studying only elimination.
We take a number of blood sample at different times (measure plasma concentration of the drug) and draw the following graph which represents the plasma concentration of drug against time.
The blood level of the drug falls in a monophasic fashion,represents a phase of drug elimination (this indicate one compartment model)



100
Plasma Concentration of the Drug
µg/ml

120
0
Time (min)

Plasma Concentration of drug/time

The blood level of the drug falls in a biphasic fashion. The initial rapid fall reflects mainly drug distribution from central to peripheral compartment the second fall represents a phase of drug elimination (this indicate two compartment model)



100
Plasma Concentration of the Drug
µg/ml

120

Time (min)

0

Plasma Concentration of drug/time

First order kinetics:
The processes of absorption, metabolism and elimination are proportional to the concentration of the drug present in the body.
First order elimination: mean constant fraction of drug eliminated per time.
The majority of drugs used therapeutically follow first order kinetics.

Zero order kinetics (saturated kinetics):

Some processes of pharmacokinetic are independent of the concentration of drug.
For some drugs as ethanol, phenytoin and salicylates which are inactivated by metabolism, the drug is removed at constant rate that is independent of plasma concentration.
The explanation for this is that the rate of metabolism of these drugs reaches a maximum after which no increase in the metabolism of the drug; this is because there is a limited amount of the enzymes which are responsible for drug metabolism.