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Vural Ozdemir, Centre for Addiction and Mental Health, University of Toronto, Canada; Department of Pharmacology, University of Toronto, Canada,
Angela D.M. Kashuba, School of Pharmacy, University of North Carolina, Chapel Hill, USA,
Vincenzo S. Basile, Centre for Addiction and Mental Health, University of Toronto, Canada,
James L. Kennedy, Centre for Addiction and Mental Health, University of Toronto, Canada
Bernard Lerer, Hadassah-Hebrew Medical Center, Jerusalem
Drug metabolism is a critical determinant of therapeutic and adverse effects of many psychotropic drugs. This chapter reviews the basic concepts and definitions pertinent to pharmacogenetics of psychotropic drug metabolism from a clinical psychiatry perspective. It discusses the CYP2D6 genetic polymorphism as a classic example of a monogenic variation in drug metabolism and as a high-affinity and low-capacity elimination route. In addition to genetic contribution to interindividual differences in drug metabolism, the chapter reviews various sources of intraindividual variations and gene-environment interactions of relevance for psychopharmacology. It highlights some of the future research directions in psychotropic drug metabolism and emphasizes the need to evaluate genetic variability in drug metabolism in conjunction with other genes encoding drug transporters, receptors and ion channels, which can all influence individual's risk for adverse drug reactions or therapeutic failure.
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