alexa Functional pharmacogenetics genomics of human cytochromes P450 involved in drug biotransformation.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Pharmacogenomics & Pharmacoproteomics

Author(s): Zanger UM, Turpeinen M, Klein K, Schwab M

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Abstract We investigated the elimination routes for the 200 drugs that are sold most often by prescription count in the United States. The majority (78\%) of the hepatically cleared drugs were found to be subject to oxidative metabolism via cytochromes P450 of the families 1, 2 and 3, with major contributions from CYP3A4/5 (37\% of drugs) followed by CYP2C9 (17\%), CYP2D6 (15\%), CYP2C19 (10\%), CYP1A2 (9\%), CYP2C8 (6\%), and CYP2B6 (4\%). Clinically well-established polymorphic CYPs (i.e., CYP2C9, CYP2C19, and CYP2D6) were involved in the metabolism of approximately half of those drugs, including (in particular) NSAIDs metabolized mainly by CYP2C9, proton-pump inhibitors metabolized by CYP2C19, and beta blockers and several antipsychotics and antidepressants metabolized by CYP2D6. In this review, we provide an up-to-date summary of the functional polymorphisms and aspects of the functional genomics of the major human drug-metabolizing cytochrome P450s, as well as their clinical significance. This article was published in Anal Bioanal Chem and referenced in Journal of Pharmacogenomics & Pharmacoproteomics

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