The Personalization of Clopidogrel Antiplatelet Therapy: The Role of Integrative Pharmacogenetics and Pharmacometabolomics.
The Personalization of Clopidogrel Antiplatelet Therapy: The Role of Integrative Pharmacogenetics and Pharmacometabolomics.
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DOI：
10.1155/2017/8062796
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发表时间：
2017
影响因子：
2.1
通讯作者：
Ibrahim B
中科院分区：
文献类型：
--
作者：
Amin AM;Sheau Chin L;Azri Mohamed Noor D;Sk Abdul Kader MA;Kah Hay Y;Ibrahim B
阿司匹林和氯吡格雷双重抗血小板治疗是经皮冠状动脉介入治疗患者的关键。然而，不同的血小板对氯吡格雷的反应性可能导致结局失败和心血管事件的复发。尽管许多遗传和非遗传因素是已知的，但很大一部分氯吡格雷可变血小板反应性仍然无法解释，这对氯吡格雷治疗的个体化提出了挑战。目前用于氯吡格雷个体化的方法包括CYP2C19基因分型、药代动力学和血小板功能测试。然而，这些方法缺乏对氯吡格雷结局的精确预测，往往导致预测不足。药物代谢组学是一种在生物体液中发现新的药物反应或毒性生物标志物的方法，已被研究用于预测药物反应。药物代谢组学的优势在于它不仅可以预测反应，还可以提供与反应有关的代谢途径的广泛信息。药物遗传学与药物代谢组学的结合可以深入了解与反应相关的未知遗传和非遗传因素。本综述旨在回顾与氯吡格雷可变血小板反应性相关因素的文献，以及评价目前氯吡格雷个体化治疗的方法。我们还回顾了药物代谢组学方法预测氯吡格雷疗效的文献，并讨论了药物代谢组学方法预测氯吡格雷疗效的可行性。
Dual antiplatelet therapy of aspirin and clopidogrel is pivotal for patients undergoing percutaneous coronary intervention. However, the variable platelets reactivity response to clopidogrel may lead to outcome failure and recurrence of cardiovascular events. Although many genetic and nongenetic factors are known, great portion of clopidogrel variable platelets reactivity remain unexplained which challenges the personalization of clopidogrel therapy. Current methods for clopidogrel personalization include CYP2C19 genotyping, pharmacokinetics, and platelets function testing. However, these methods lack precise prediction of clopidogrel outcome, often leading to insufficient prediction. Pharmacometabolomics which is an approach to identify novel biomarkers of drug response or toxicity in biofluids has been investigated to predict drug response. The advantage of pharmacometabolomics is that it does not only predict the response but also provide extensive information on the metabolic pathways implicated with the response. Integrating pharmacogenetics with pharmacometabolomics can give insight on unknown genetic and nongenetic factors associated with the response. This review aimed to review the literature on factors associated with the variable platelets reactivity response to clopidogrel, as well as appraising current methods for the personalization of clopidogrel therapy. We also aimed to review the literature on using pharmacometabolomics approach to predict drug response, as well as discussing the plausibility of using it to predict clopidogrel outcome.