The influence of omeprazole on platelet inhibition of clopidogrel in various CYP2C19 mutant alleles.
The influence of omeprazole on platelet inhibition of clopidogrel in various CYP2C19 mutant alleles.
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DOI：
10.1089/gtmb.2012.0119
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发表时间：
2012-10
影响因子：
1.4
通讯作者：
Qian Liu;Da-sheng Dang;Yu-feng Chen;Ming Yan;Guo-bing Shi;Qingchun Zhao
中科院分区：
文献类型：
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作者：
Qian Liu;Da-sheng Dang;Yu-feng Chen;Ming Yan;Guo-bing Shi;Qingchun Zhao
目前，氯吡格雷和质子泵抑制剂（尤其是奥美拉唑）相互作用的问题正在增加，因为它们都是通过CYP 2C 19代谢的。此外，奥美拉唑还能抑制CYP 2C 19的活性。本研究旨在比较奥美拉唑对不同CYP 2C 19突变等位基因的氯吡格雷血小板抑制作用的影响。142例连续接受选择性冠状动脉支架植入术的患者接受阿司匹林和氯吡格雷治疗，并随机接受奥美拉唑或安慰剂治疗。分析入组患者的二磷酸腺苷诱导的血小板聚集（ADP-Ag），并通过聚合酶链反应-限制性片段长度多态性鉴定CYP 2C 19 *2和CYP 2C 19 *3。在纳入的患者中，47例（33.1%）属于纯合子快代谢型（homEM）（CYP 2C 19 *1/*1），70例（49.3%）属于杂合子快代谢型（hetEM）（*1/*2或 *1/*3），25例（17.6%）属于慢代谢型（PM）（*2/*3或 *2/*2）。ADP-Ag在3个基因型组间差异有统计学意义（p0.05）。总之，在CYP 2C 19 homEM中，奥美拉唑合并治疗似乎最显著地降低了氯吡格雷的抗血小板作用。
Currently, concerns of clopidogrel and proton pump inhibitors (especially omeprazole) interaction are raised, because they are both metabolized by CYP2C19. What is more, omeprazole can also inhibit the activity of CYP2C19. The study was to compare the influence of omeprazole on platelet inhibition of clopidogrel in various CYP2C19 mutant alleles. One hundred forty-two consecutive patients undergoing elective coronary stenting received aspirin and clopidogrel, and were randomized to omeprazole or the placebo. Enrolled patients were analyzed for adenosine diphosphate-induced platelet aggregation (ADP-Ag), and CYP2C19*2 and CYP2C19*3 were identified by polymerase chain reaction-restriction fragment length polymorphism. Of the patients included, 47 (33.1%) belonged to homozygous extensive metabolizers (homEMs) (CYP2C19*1/*1), 70 (49.3%) belonged to heterozygous extensive metabolizers (hetEMs) (*1/*2 or *1/*3), and 25 (17.6%) belonged to poor metabolizers (PMs) (*2/*3 or *2/*2). ADP-Ag had a significant difference among the three genotypic groups (p0.05). In conclusion, concomitant therapy with omeprazole appears to reduce the antiplatelet effect of clopidogrel most significantly in homEMs of CYP2C19.