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

被引：475

作者：

Zanger, Ulrich M. ^{[1
,2
]}

Turpeinen, Miia ^{[1
,2
,3
]}

Klein, Kathrin ^{[1
,2
]}

Schwab, Matthias ^{[1
,2
]}

机构：

[1] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany

[2] Univ Tubingen, Dept Clin Pharmacol, Tubingen, Germany

[3] Univ Oulu, Dept Pharmacol & Toxicol, Oulu 90014, Finland

来源：

ANALYTICAL AND BIOANALYTICAL CHEMISTRY | 2008年 / 392卷 / 06期

基金：

芬兰科学院;

关键词：

Drug metabolism; Functional genomics; Genotype; Mutation; Pharmacogenetics; Phenotype; Single-nucleotide polymorphism;

D O I：

10.1007/s00216-008-2291-6

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1093 / 1108

页数：16

共 246 条

[51]

Fuhr U, 2005, INT J CLIN PHARM TH, V43, P327

[52] Effect of genotypic differences in CYP2C19 on cure rates for Helicobacter pylori infection by triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin [J].