Polymorphic human cytochrome P450 enzymes: an opportunity for individualized drug treatment

Approximately 40% of human P450-dependent drug metabolism is carried out by polymorphic enzymes, which can cause abolished, quantitatively or qualitat ively altered or enhanced drug metabolism. The latter situation is due to s table duplication, multiduplication or amplification of active genes, most likely in response to dietary components that have resulted in a selection of alleles with multiple non-inducible genes. Several examples exist where subjects carrying certain alleles suffer from a lack of drug efficacy due t o ultrarapid metabolism or, alternatively, adverse effects from the drug tr eatment due to the presence of defective alleles. Knowledge in this field h as grown rapidly and can now be applied to both drug development and clinic al practice. This is facilitated by the recent development of high-throughp ut methods for mutation detection and oligonucleotide chips array technolog y for the identification of a multitude of mutations in the genes encoding drug-metabolizing enzymes. The outcome will allow for safer and more effici ent drug therapies.