Shin Jaekyu
Department of Clinical Pharmacy, School of Pharmacy, University of California, San Francisco, CA 94143, USA.
J Pharm Pract. 2012 Aug;25(4):428-38. doi: 10.1177/0897190012448310. Epub 2012 Jun 6.
Genetic polymorphisms significantly influence responses to warfarin and clopidogrel. Polymorphisms in the cytochrome P450 (CYP) 2C9 and vitamin K epoxide reductase genes change warfarin pharmacokinetics and pharmacodynamics, respectively. Because these polymorphisms influence warfarin dose requirements, they may primarily help determine therapeutic warfarin doses in patients who newly start on the drug. To assist in estimating therapeutic warfarin doses, the warfarin label provides a pharmacogenomic dosing table and various warfarin pharmacogenomic dosing algorithms are available. On the other hand, polymorphisms in the CYP2C19 gene affect clopidogrel pharmacokinetics. These polymorphisms may be useful to identify clopidogrel nonresponders who may benefit from taking an alternative antiplatelet agent such as prasugrel and ticagrelor. Although both drugs have pharmacogenomic tests available for clinical use, their clinical utilities have not been established and are currently being actively studied. In this review, clinical application of warfarin and clopidogrel pharmacogenomics will be focused. With the current level of evidence, potential patients who may get benefit from warfarin and clopidogrel pharmacogenomic testing will be discussed. In addition, the interpretation of the warfarin and clopidogrel test results and the current barriers to widespread use of warfarin and clopidogrel pharmacogenomic testing will be discussed.
基因多态性显著影响对华法林和氯吡格雷的反应。细胞色素P450(CYP)2C9和维生素K环氧化物还原酶基因的多态性分别改变华法林的药代动力学和药效动力学。由于这些多态性影响华法林的剂量需求,它们可能主要有助于确定新开始使用该药物的患者的华法林治疗剂量。为了帮助估计华法林治疗剂量,华法林标签提供了一个药物基因组学给药表,并且有各种华法林药物基因组学给药算法可供使用。另一方面,CYP2C19基因的多态性影响氯吡格雷的药代动力学。这些多态性可能有助于识别可能从服用替代抗血小板药物(如普拉格雷和替格瑞洛)中获益的氯吡格雷无反应者。虽然这两种药物都有可用于临床的药物基因组学检测,但它们的临床实用性尚未确立,目前正在积极研究中。在本综述中,将重点关注华法林和氯吡格雷药物基因组学的临床应用。基于目前的证据水平,将讨论可能从华法林和氯吡格雷药物基因组学检测中获益的潜在患者。此外,还将讨论华法林和氯吡格雷检测结果的解读以及目前华法林和氯吡格雷药物基因组学检测广泛应用的障碍。