Pharmacogenetics of drug metabolising enzymes: Importance for personalised medicine

被引:47
作者
Oscarson, M [1 ]
机构
[1] Univ Basel, Bioctr, Div Pharmacol Neurobiol, CH-4056 Basel, Switzerland
关键词
pharmacogenetics; genetic polymorphism; drug metabolising enzymes; cytochrome P450s; thiopurine-S-methyltransferase;
D O I
10.1515/CCLM.2003.087
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
The number of polymorphisms identified in genes encoding drug metabolising enzymes, drug transporters, and receptors is rapidly increasing. In many cases, these genetic factors have a major impact on the pharmacokinetics and pharmacodynamics of a particular drug and thereby influence the sensitivity to such drug in an individual patient with a certain genotype. The highest impact is seen for drugs with a narrow therapeutic index, with important examples emerging from treatment with antidepressants, oral anticoagulants, and cytostatics, which are metabolised by the polymorphic enzymes cytochrome P450 2D6 (CYP2D6), cytochrome P450 2C9 (CYP2C9), and thiopurineSmethyltransferase (TPMT), respectively. In order to apply the increasing amount of pharmacogenetic knowledge to clinical practise, specific dosage recommendations based on genotypes will have to be developed to guide the clinician, and these recommendations will have to be evaluated in prospective clinical studies. Such development will lead to a patienttailored drug therapy which hopefully would be more efficient and will result in fewer adverse drug reactions.
引用
收藏
页码:573 / 580
页数:8
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