摘要
香豆素衍生物是常见的抗凝血剂处方,常用于血栓栓塞的预防与治疗。由于治疗指数狭窄以及病人之间和病人自身使用剂量上大的差异,香豆素的治疗仍具有挑战性,特别是在治疗初期。广泛的证据表明结合大量的临床因素在CYP2C9和VKPRC1中常见的基因变异是香豆素剂量多样化的重要决定因素。对包含遗传和非遗传因素的药理基因的不断研究,使香豆素在初期治疗安全性有所改善。近期,三种随机对照的抗凝血剂、苊香豆醇以及苯丙香豆素的剂量药理基因的试验研究(COAG 和 EU-PACT 实验) 已经发表。在这些试验中,不同香豆素剂量策略进行了对照,以判断药理基因的测试是否有利于香豆素剂量的控制。这篇综述的目的在于呈现和讨论目前出版的随机对照的试验研究的设计与结果,并解决香豆素的药理基因学研究到临床实践的问题。
关键词: 苊香豆醇,COAG,CYP2C9,EU-PACT,药物遗传学,苯丙香豆素,VKORC1,华法林
Current Molecular Medicine
Title:The COAG and EU-PACT Trials: What is the Clinical Benefit of Pharmacogenetic-Guided Coumarin Dosing During Therapy Initiation?
Volume: 14 Issue: 7
Author(s): E.V. Baranova, F.W. Asselbergs, A. de Boer and A.H. Maitland-van der Zee
Affiliation:
关键词: 苊香豆醇,COAG,CYP2C9,EU-PACT,药物遗传学,苯丙香豆素,VKORC1,华法林
摘要: Coumarin derivates are oral anticoagulants commonly prescribed for treatment and prevention of thromboembolism. Due to a small therapeutic index and large inter- and intrapatient differences in dose requirements, treatment with coumarins is challenging, particularly in its starting phase. Extensive evidence suggests that common genetic variants in CYP2C9 and VKORC1 genes together with a number of clinical factors are important determinants of the coumarin dose variability. Pharmacogenetic algorithms comprising both genetic and non-genetic factors were developed to improve the safety of coumarin therapy initiation. Recently, three randomized controlled trials (the COAG and the EU-PACT trials) on pharmacogenetic dosing of warfarin, acenocoumarol and phenprocoumon were published. In these trials different coumarin dosing strategies were compared to investigate whether or not pharmacogenetic testing could be beneficial for coumarin management. The purpose of this review was to present and discuss the design and results of these studies within the context of previously published randomized controlled trials and to address the issues surrounding the incorporation of coumarin pharmacogenetic testing into clinical practice.
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Baranova E.V., Asselbergs F.W., Boer de A. and Zee Maitland-van der A.H., The COAG and EU-PACT Trials: What is the Clinical Benefit of Pharmacogenetic-Guided Coumarin Dosing During Therapy Initiation?, Current Molecular Medicine 2014; 14 (7) . https://dx.doi.org/10.2174/1566524014666140811114906
DOI https://dx.doi.org/10.2174/1566524014666140811114906 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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