[Clinical relevance of drug metabolism polymorphisms]

Individual variation in drug response is a substantial clinical problem. Research in pharmacogenetics is currently evolving in two directions, firstly to identify genes and gene products associated with certain diseases, which may serve as targets for new drugs, and secondly to identify genes and allelic variants of genes that affect the expected and adverse response to current and future drugs. In that respect drug metabolising enzymes play a key role. A readily and widely available pheno- and/or genotyping service for drug metabolism polymorphisms is currently not established and the clinical relevance has only been shown for a limited number of drugs. The overall pharmacologic effects are typically not monogenic traits, they are a result of an interaction of several genes encoding proteins involved in drug metabolism, disposition, and effects. Each individual represents a unique combination of polymorphic genes that are known to be involved in the metabolism and disposition of medications, in the target structures of drug therapy, and in the pathogenesis of diseases. This will lead to the development of DNA chips for genotyping which will guide the selection and dosing of drug therapy in the future.