pharmacology

DRUG CLEARANCE THROUGH METABOLISM
Once a drug enters the body, the process of elimination begins. The three
major routes of elimination are hepatic metabolism, biliary elimination,
and urinary elimination. Together, these elimination processes decrease
the plasma concentration exponentially. That is, a constant fraction of the
most drug present is eliminated in a given unit of time
drugs are eliminated according to first-order kinetics, although some,
such as aspirin in high doses, are eliminated according to zero-order
or nonlinear kinetics. Metabolism leads to production of products with
increased polarity, which allows the drug to be eliminated. Clearance
(CL) estimates the amount of drug cleared from the body per unit of time.
Total CL is a composite estimate reflecting all mechanisms of drug elimination
and is calculated as follows:
t1/ 2= 0 693 *Vd / cl
where t1/2 is the elimination half-life, Vd is the apparent volume of distribution,
and 0.693 is the natural log constant. Drug half-life is often used as
a measure of drug CL, because, for many drugs, Vd is a constant.
Kinetics of metabolism
1. First-order kinetics: The metabolic transformation of drugs is
catalyzed by enzymes, and most of the reactions obey Michaelis-Menten kinetics.
2. Zero-order kinetics: With a few drugs, such as aspirin, ethanol,
and phenytoin, the doses are very large. Therefore, [C] is much
greater than Km, and the velocity equation becomes
The enzyme is saturated by a high free drug concentration,
and the rate of metabolism remains constant over time. This is
called zero-order kinetics (also called nonlinear kinetics). A constant