Pharmacogenetics

Abstract

Inter-individual variability in drug response is a major clinical problem. Adverse drug reactions (ADRs) are common, are responsible for a number of debilitating side effects following drug therapy and are a significant cause of death. It is now clear that much of the observed variability in drug response has a genetic basis, arising as a result of genetically-determined differences in drug absorption, disposition, metabolism or excretion. The best characterised pharmacogenetic polymorphisms are those within the phase I cytochrome P450 family of drug metabolising enzymes. One of these enzymes, CYP2D6 (debrisoquine hydroxylase), metabolizes one-quarter of all prescribed drugs and is inactive in 6% of the Caucasian population. Individuals at risk of developing ADRs as a result of genetically-determined variation in genes such as CYP2D6 can now be identified using DNA-based tests. A detailed knowledge of the genetic basis of individual drug response is potentially of major clinical and economic importance and could provide the basis for a rational approach to drug prescription. This would have significant benefits for human health.