[Pharmacogenomics: the quest for individualized therapy]

Different patients exhibit wide variability in the way they respond to medications. Individual differences in drug response can result from environmental factors, as well as genetic determinants. In particular, inherited differences in the metabolism and disposition of drugs can have a great influence on the efficacy and toxicity of medications, so herein we focus on the pharmacogenetics of drug metabolism.

Clinical observations of inherited differences in drug effects were first documented in the 1950s, giving rise to the field of pharmacogenetics. These observations were then followed by population studies of drug disposition phenotype, then biochemical, and eventually molecular elucidation of the genetic defect associated with the inherited trait. Genetic polymorphisms have been described for many phase I and phase II drug-metabolizing enzymes including several cytochromes P450, N-acetyltransferases, and thiopurine S-methyltransferase. Rapid advances in human genomics gave birth to pharmacogenomics, an emerging discipline that uses genome-wide approaches to study the entire spectrum of genes involved in drug response. High-through-put genomic technologies will serve as the foundation of personalized therapies.

Knowledge of an individual's genetic variability in drug response may be clinically and economically important and could provide the basis for a rational approach to drug prescription in neuropsychiatric disorders.