Molecular genetics of CYP2D6: Clinical relevance with focus on psychotropic drugs
Article first published online: 18 JAN 2002
British Journal of Clinical Pharmacology
Volume 53, Issue 2, pages 111–122, February 2002
How to Cite
Bertilsson, L., Dahl, M.-L., Dalén, P. and Al-Shurbaji, A. (2002), Molecular genetics of CYP2D6: Clinical relevance with focus on psychotropic drugs. British Journal of Clinical Pharmacology, 53: 111–122. doi: 10.1046/j.0306-5251.2001.01548.x
- Issue published online: 18 JAN 2002
- Article first published online: 18 JAN 2002
- Received 23 February 2001, accepted 24 October 2001.
Cytochrome P450 CYP2D6 is the most extensively characterized polymorphic drug-metabolizing enzyme. A deficiency of the CYP2D6 enzyme is inherited as an autosomal recessive trait; these subjects (7% of Caucasians, about 1% of Orientals) are classified as poor metabolizers. Among the rest (extensive metabolizers), enzyme activity is highly variable, from extremely high in ultrarapid metabolizers, to markedly reduced in intermediate metabolizers. The CYP2D6 gene is highly polymorphic, with more than 70 allelic variants described so far. Of these, more than 15 encode an inactive or no enzyme at all. Others encode enzyme with reduced, ‘normal’ or increased enzyme activity. The CYP2D6 gene shows marked interethnic variability, with interpopulation differences in allele frequency and existence of ‘population-specific’ allelic variants, for instance among Orientals and Black Africans. The CYP2D6 enzyme catalyses the metabolism of a large number of clinically important drugs including antidepressants, neuroleptics, some antiarrhythmics, lipophilic β-adrenoceptor blockers and opioids. The present-day knowledge on the influence of the genetic variability in CYP2D6 on the clinical pharmacokinetics and therapeutic effects/adverse effects of psychotropic drugs is reviewed.