Genetic polymorphism of cytochrome P450 enzymes in Asian populations: focus on CYP2D6.

Published studies demonstrate that significant ethnic differences can exist in the metabolism of some drugs. These differences are caused by cytochrome P450 polymorphisms and result in the potential for wide interpatient and interethnic variability in adverse events. One of the most common of these cytochrome P450 polymorphisms is related to the CYP2D6 isozyme. Many classes of commonly used drugs are metabolized by CYP2D6, creating the potential for significant adverse events. Due to the variety of genetic polymorphisms among Asian populations, this article focuses on this group rather than on other ethnic populations and discusses the clinical importance of genetic polymorphisms with regard to potential drug interactions. Polymorphism of CYP2D6 can either increase the rate of drug elimination (ultrametabolizers, leading to faster metabolic clearance potentially resulting in reduced effectiveness and need for higher doses) or decrease drug metabolism (poor metabolizers, which may increase the potential for drug interactions and adverse events). Although the CYP2D6 poor metabolizer phenotype is less frequent in Asian than in Western populations (e.g. about 1% in Thai, Chinese and Japanese populations and up to 4.8% in Indians versus 5-10% in Caucasians), the increased prevalence of the CYP2D6*10 allele in Asians does have an impact on drugs metabolized by CYP2D6. Enzyme activity is reduced, potentially increasing circulating drug doses and increasing the risk for drug interactions. Thus, in Asian populations it may be important to optimize pharmacotherapy either by assessing patients' CYP2D6 genotype, or by prescribing medications that are not metabolized by this isozyme.