Authors: Dorado, P.; Berecz, R.; Penas-Lledo, E. M.; Caceres, M. C.; Llerena, A.

Source: Current Drug Targets, Volume 7, Number 12, December 2006 , pp. 1671-1680(10)

Publisher: Bentham Science Publishers

Abstract:

CYP2D6 is described as the most relevant enzyme in the metabolism of many antipsychotic drugs. Its contribution to the interindividual differences in drug response is reviewed here highlighting its role in the kinetics of antipsychotic drugs and the occurrence of drug interactions.

The activity of CYP2D6 is inherited as a monogenetic trait and the CYP2D6 gene appears highly polymorphic in humans. The polymorphic alleles may lead to altered activity of the CYP enzymes causing absent, decreased (poor), or increased (ultrarapid) metabolism that in turn influence the disposition of the antipsychotic drugs. Antipsychotic drug biotransformation is mainly determined by genetic factors mediating CYP2D6 gene polymorphism, however the importance of environmental factors (dietary, smoking, diseases, etc.) is also recognized. Additionally, the potential interaction between CYP2D6 and the endogenous metabolism must be taken into consideration.

The present review summarizes the relevance of physiological and environmental factors in CYP2D6 hydroxylation capacity, the inhibition of CYP2D6 activity during treatment, the use of drug/metabolite ratio as a tool to evaluate CYP2D6 hydroxylation capacity in a patient, and the relevance of CYP2D6 for drug plasma concentration and for QTc interval lengthening during treatment with antipsychotic drugs.

Keywords: pharmacogenetics; antipsychotic drugs; CYP2D6; pharmacogenomics

Document Type: Research article

DOI: http://dx.doi.org/10.2174/138945006779025329

Affiliations: 1: University of Extremadura,Faculty of Medicine. Avda. de Elvas s/n. E-06071, Badajoz, Spain.

Publication date: 2006-12-01

More about this publication?

• Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will be devoted to a single timely topic, with series of in-depth reviews, written by leaders in the field, covering a range of current topics on drug targets. These issues will be organized and led by a guest editor who is a recognized expert in the overall topic. As the discovery, identification, characterisation and validation of novel human drug targets for drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.

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