摘要
氯吡格雷作为抗血小板聚集药物,尤其在急性冠状动脉综合征、经皮冠状动脉介入术后治疗时发挥重要作用。然而在临床给药过程中发现,易出现氯吡格雷抵抗。参与氯吡格雷反应抵抗的因素很多,目前的关注点主要集中在CYP450酶基因多态性与氯吡格雷抵抗的研究,有关转运体和受体结合位点基因多态性的综述较少,更少见高原人群、不同民族人群间的基因多态性研究。本研究主要从药物吸收转运体的基因多态性与氯吡格雷生物利用度的关系,药物代谢酶对氯吡格雷的生物转化,氯吡格雷活性代谢产物与受体结合发挥药效的全过程进行综述,吸收转运体ABCB1基因位点突变会影响氯吡格雷的生物利用度;代谢酶基因多态性中起关键作用的是CYP2C19和CES1,应根据基因分型调整剂量;生物学活性基因P2Y12基因多态性会影响氯吡格雷的疗效。因此,掌握氯吡格雷基因多态性的影响因素,有助于氯吡格雷的个体化给药,以最大限度地减少抗血小板效应不足导致的血栓性事件或抗血小板效应过度导致的出血性事件。
Clopidogrel plays an important role in anti-platelet aggregation, especially in acute coronary syndrome and percutaneous coronary intervention. However, elopidogrel resistance is common in clinical treatment. There are many factors response to elopidogrel resistance. Current researches concentrated in CYP450 enzyme gene polymorphism with clopidogrel resistance. There are few reviews on genetic polymorphisms of transporter and receptor binding sites, furthermore, the gene polymorphisms among different ethnic groups in plateau populations are very rare. In this paper, we mainly reviewed the relationship between gene polymorphism of drug-transporter and bioavailability of clopidogrel, the whole process of drug-metabolizing enzyme＇s bioconversion of clopidogrel and the active metabo-lite of clopidogrel combine with the receptors. A mutation in the ABCB1 gene of the transporter was found to affect the bioavailability of clopidogrel. The key role of polymorphisms in the metabolic enzyme gene is CYP2C19 and CES1. The dose should be adjusted according to genotyping. The biologically active gene P2Y12 polymorphism affects the efficacy of clopidogrel. Therefore, understanding the clopidogrel gene polymorphism influencing factors can help individualized administration of clopidogrel to minimize thrombotic events caused by insufficient antiplatelet effect or hemorrhagic events caused by excessive anti-platelet effect.
作者
孙月梅
崔明霞
李文斌
张娟红
陈玉艳
鹿辉
王昌
王荣
SUN Yue-mei;CUI Ming-xia;LI Wen-bin;ZHANG Juan-hong;CHEN Yu-yan;LU Hui;WANG Chang;WANG Rong(College of Basic Medical Sciences,Lanzhou University,Lanzhou 730000,China;PLA Key Laboratory of The Plateau of the Environmental Damage Control,Lanzhou General Hospital,Lanzhou Command,Lanzhou 730050,China)
出处
《中国药学杂志》
CAS
CSCD
北大核心
2018年第18期1529-1535,共7页
Chinese Pharmaceutical Journal
基金
国家自然科学基金项目资助(81403004
81673508
81401552)
全军后勤科研"十二五"重大项目资助(AWS14L0005)
国家科技重大专项资助项目(2008ZXJ09014-010)
全军医学科研"十二五"重点项目资助(BWS12J012)
甘肃省自然基金项目资助(145RJZA111
1606RJZA176)
兰州大学中央高校基本科研业务费专项资金项目资助(lzujbky-2017-141)
关键词
氯吡格雷
氯吡格雷抵抗
基因多态性
生物转化
个体化给药
elopidogrel
clopidogrel resistance
gene polymorphism
bioconversion
individualized administration
