Pharmacogenetics 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 7%-10% of Caucasians lack any CYP2D6 activity due to deletions and frame-shift or splice-site mutations of the gene. 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.
Cascorbi
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Institute of Pharmacology, Ernst Moritz Arndt University Greifswald, Germany. cascorbi@uni-greifswald.de
D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000502:physiology; D005006:Ethnicity; D006801:Humans; D010599:Pharmacokinetics; D011110:Polymorphism, Genetic
D019389:Cytochrome P-450 CYP2D6