European journal of clinical investigation
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Eur. J. Clin. Invest. · Nov 2003
ReviewPharmacogenetics of cytochrome p4502D6: genetic background and clinical implication.
Interindividual differences in the pharmacokinetics of a number of drugs are often due to hereditary polymorphisms of drug-metabolizing enzymes. Most important is cytochrome p4502D6 (CYP2D6), also known as debrisoquine/sparteine hydroxylase. It catalyzes hydroxylation or demethylation of more than 20% of drugs metabolized in the human liver, such as neuroleptics, antidepressants, some beta-blockers and many others like codeine. ⋯ About 1%-3% of Middle-Europeans, but up to 29% of Ethiopians display gene duplications, leading to elevated so-called ultrarapid metabolization rates. Meanwhile there is now a much better understanding of the genetic background of poor, intermediate, extensive and ultrarapid metabolizers, enabling a more precise DNA genotyping-based prediction of plasma levels. Since there is evidence that deteriorated drug elimination partly accounts for drug side-effects, CYP2D6 genotyping could contribute to an individualized and therefore optimized drug therapy.