Polymorphic metabolism by functional alterations of human cytochrome P450 enzymes.

The study of cytochrome P450 pharmacogenomics is of particular interest because of its promise in the development of rational means to optimize drug therapy with respect to patient's genotype to ensure maximum efficacy with minimal adverse effects. Drug metabolizing P450 enzymes are polymorphic and are the main phase I enzymes responsible for the metabolism of clinical drugs. Therefore, polymorphisms in the P450s have the most impact on the fate of clinical drugs in phase I metabolism since almost 80% of drugs in use today are metabolized by these enzymes. Predictive genotyping for P450 enzymes for a more effective therapy will be routine for specific drugs in the future. In this review, we discuss the current knowledge of polymorphic metabolism by functional alterations in nonsynonymous SNPs of P450 1A2, 2A6, 2C8, 2C9, 2C19, 2D6, and 3A4 enzymes.