GENETIC-POLYMORPHISM OF DRUG-METABOLIZING-ENZYMES IN AFRICAN POPULATIONS - IMPLICATIONS FOR THE USE OF NEUROLEPTICS AND ANTIDEPRESSANTS

Metabolism of most drugs influences their pharmacological and toxicolo gical effects, Drugs particularly affected are those with a narrow the rapeutic window and that are subjected to considerable first-pass meta bolism. Much of the interindividual and interethnic differences in eff ects of drugs is now attributable to genetic differences in their meta bolism. Genetic polymorphisms have been described for many drug-metabo lising enzymes in Caucasian and Oriental populations, the most well-ch aracterised being those for cytochrome P450 2D6, cytochrome P450 2C19, glutathione S-transferases, and N-acetyl transferase 2. African popul ations have been studied to a lesser extent, but it is apparent that p opulations within Africa are heterogeneous with respect to these polym orphisms, In addition, although some allelic variants are common to al l populations throughout the world (e.g., CYP2D65), some allelic vari ants are specific for an African population (e.g., CYP2D617), The pol ymorphisms give rise to enzymes with changed or no activity towards dr ug substrates. Two of the most important enzymes for metabolism of neu roleptics and other psychoactive drugs are CYP2D6 and CYP2C19. This ar ticle compares the current information on polymorphisms of these two e nzymes in African and other populations and discusses the implications of these polymorphisms for neuropharmacotherapy. (C) 1997 Elsevier Sc ience Inc.