Drug metabolizing enzymes are of paramount importance in drug detoxification as well as chemical mutagenesis, carcinogenesis and toxicity mediated via metabolic activation. Thus genetically determined differences in the activity of these enzymes can influence individual susceptibility to adverse drug reactions, drug induced diseases and certain types of chemically induced cancers. The genetic polymorphisms of three human drug metabolising enzymes, namely N-acetyltransferase and two cytochrome P450 isozymes (P-450IID6: debrisoquine / sparteine polymorphism, P-450IIC10: mephenytoin polymorphism) have been firmly established. Based on the metabolic handling of certain probe drugs the population can be divided into two phenotypes: the rapid acetylator / extensive metabolizer and slow acetylator / poor metabolizer. These polymorphisms have provided useful tools for the study of the relationship between genetically determined differences in the activity of drug metabolizing enzymes and the risk of adverse drug reactions and certain types of chemically induced diseases and cancers.
