Pharmacogenomics in Drug Metabolism Enzymes and Transporters

The safe and effective use of drug therapies play a critical role in treating disease. Interindividual variability in drug metabolism and transport can have a major impact on the efficacy and adverse effects associated with drug therapies. Various drug metabolizing enzymes, such as cytochrome P450 (CYP) enzymes, and drug transporter proteins are essential for drug delivery and elimination. Genes encoding these enzymes and transporters (pharmacogenes) can be highly variable with allele distribution showing considerable differences among geographically and ethnically diverse populations. Variation in pharmacogenes can have a significant impact on the absorption and elimination of substrate drugs, which may lead to increased risk for therapeutic failure or adverse events. This chapter will briefly review the history surrounding the emergence of present-day pharmacogenomics as well as foundational concepts for understanding genetic variation and associated nomenclature. In addition, the chapter will provide an up-to-date summary of the pharmacogenetics of major drug-metabolizing enzymes and transporters, and discuss the clinical impact of pharmacogene variants.