Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation

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...

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Bibliographic Details
Published in:Analytical and bioanalytical chemistry 2008-11, Vol.392 (6), p.1093-1108
Main Authors: Zanger, Ulrich M, Turpeinen, Miia, Klein, Kathrin, Schwab, Matthias
Format: Article
Language:English
Subjects:
Adrenergic beta-Antagonists - pharmacology
Analytical Chemistry
Beta
Biochemistry
Biotransformation
Characterization and Evaluation of Materials
Chemistry
Chemistry and Materials Science
Counting
Cytochrome P-450 Enzyme System - classification
Cytochrome P-450 Enzyme System - genetics
Cytochrome P-450 Enzyme System - metabolism
Cytochromes P450
Drug Design
Drug metabolism
Drugs
Food Science
Functional genomics
Genomics - methods
Genotype
Human
Humans
Inhibitors
Laboratory Medicine
Mathematical analysis
Metabolism
Monitoring/Environmental Analysis
Mutation
Pharmacogenetics
Pharmacogenetics - methods
Phenotype
Polymorphism, Single Nucleotide
Proton Pump Inhibitors - pharmacology
Psychotropic Drugs - pharmacology
Review
Single-nucleotide polymorphism
Technology, Pharmaceutical - methods
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Summary: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.
ISSN:1618-2642
1618-2650
DOI:10.1007/s00216-008-2291-6