PHARMACOGENETICS - A LABORATORY TOOL FOR OPTIMIZING THERAPEUTIC EFFICIENCY

Pharmacogenetics is the study of the linkage between an individual's g enotype and that individual's ability to metabolize a foreign compound . Differences in metabolism of therapeutics can lead to severe toxicit y or therapeutic failure by altering the relation between dose and blo od concentration of the pharmacologically active drug. Phenotypes exhi biting poor and ultraextensive metabolism result from genetic variance (polymorphism) of enzymes involved in metabolism. Thus, in pharmacoge netic studies one applies genotyping of polymorphic alleles encoding d rug-metabolizing enzymes to the identification of an individual's drug metabolism phenotype. This knowledge, when applied to dosing or drug selection, can avoid adverse reactions or therapeutic failure and thus enhance therapeutic efficiency. More than 25 commonly prescribed medi cines are metabolized by the cytochrome P-4502D6 (CYP2D6) isoenzyme, a nd polymorphism of the CYP2D6 gene affects the therapeutic management of up to 17% of individuals in some ethnic groups. In this review, we summarize and update information concerning drug-metabolizing genotype s with emphasis on CYP2D6 genotyping techniques that can be applied by the clinical laboratory for linking human genetics to therapeutic man agement.