C1 Refereed scientific book
Cytochrome P450 in Pharmacogenetics: An Update
Authors: Tornio A, Backman JT
Publisher: ELSEVIER ACADEMIC PRESS INC, 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA
Publication year: 2018
Journal: Advances in Pharmacology
Journal name in source: PHARMACOGENETICS
Journal acronym: ADV PHARMACOL
Volume: 83
First page : 3
Last page: 32
Number of pages: 30
ISBN: 978-0-12-813381-1
ISSN: 1054-3589
DOI: https://doi.org/10.1016/bs.apha.2018.04.007
Abstract
Interindividual variability in drug disposition is a major cause of lack of efficacy and adverse effects of drug therapies. The majority of hepatically cleared drugs are metabolized by cytochrome P450 (CYP) enzymes, mainly in families CYP1, CYP2, and CYP3. Genes encoding these enzymes are highly variable with allele distribution showing considerable differences between populations. Genetic variability of especially CYP2C9, CYP2C19, CYP2D6, and CYP3A5 is known to have clear clinical impact on drugs that are metabolized by these enzymes. CYP1A2, CYP2A6, CYP2B6, CYP2C8, and CYP3A4 all show variability that affects pharmacokinetics of drugs as well, but so far the evidence regarding their clinical implications is not as conclusive. In this review, we provide an up-to-date summary of the pharmacogenetics of the major human drug-metabolizing CYP enzymes, focusing on clinically significant examples.
Interindividual variability in drug disposition is a major cause of lack of efficacy and adverse effects of drug therapies. The majority of hepatically cleared drugs are metabolized by cytochrome P450 (CYP) enzymes, mainly in families CYP1, CYP2, and CYP3. Genes encoding these enzymes are highly variable with allele distribution showing considerable differences between populations. Genetic variability of especially CYP2C9, CYP2C19, CYP2D6, and CYP3A5 is known to have clear clinical impact on drugs that are metabolized by these enzymes. CYP1A2, CYP2A6, CYP2B6, CYP2C8, and CYP3A4 all show variability that affects pharmacokinetics of drugs as well, but so far the evidence regarding their clinical implications is not as conclusive. In this review, we provide an up-to-date summary of the pharmacogenetics of the major human drug-metabolizing CYP enzymes, focusing on clinically significant examples.
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