功能降低的CYP2C19等位基因非携带者最易受质子泵抑制剂损害氯吡格雷抗血小板作用的影响：一项初步研究。
Non-Carriers of Reduced-Function CYP2C19 Alleles are Most Susceptible to Impairment of the Anti-Platelet Effect of Clopidogrel by Proton-Pump Inhibitors: A Pilot Study.
作者信息
Lee Jen-Kuang, Wu Cho-Kai, Juang Jyh-Ming, Tsai Chia-Ti, Hwang Juey-Jen, Lin Jiuun-Lee, Chiang Fu-Tien
机构信息
Division of Cardiology, Department of Internal Medicine; ; Department of Laboratory Medicine, National Taiwan University College of Medicine and Hospital; ; Graduate Institute of Biomedical Electronics and Bioinformatics, College of Electrical Engineering and Computer Science, National Taiwan University, Taipei, Taiwan.
Division of Cardiology, Department of Internal Medicine;
出版信息
Acta Cardiol Sin. 2016 Mar;32(2):215-22. doi: 10.6515/acs20160201a.
BACKGROUND
The phenomenon of CYP2C19 polymorphism affects the metabolism of both clopidogrel and proton-pump inhibitors (PPI). However, concomitant use of both drugs may reduce the desired therapeutic effects. In this study, we evaluated whether individuals with different numbers of reduced-function CYP2C19 alleles were equally affected and whether PPIs with different dependencies on CYP2C19 metabolism were equally involved.
METHODS
Thirty healthy volunteers were recruited to a six-week regimen of clopidogrel. Three PPIs with different metabolic dependencies on CYP2C19 were included and separately administered in this order. Each PPI was given for a week, followed by a one-week washout period before the intervention of the next PPI. The anti-platelet effect was examined by Thromboelastography Platelet Mapping(TM) (TEG®) and vasodilator-stimulated phosphoprotein (VASP) assays.
RESULTS
Both TEG® and VASP tests showed the same general qualitative trend, but TEG® detected a statistically significant fluctuation of platelet aggregation in response to different drug interventions. The TEG® results also demonstrated that non-carriers experienced the most significant impairment of anti-platelet effect of clopidogrel after concomitant use of PPIs. This impairment was closely related to the metabolic dependence on CYP2C19 of PPI.
CONCLUSIONS
Our study indicated that non-carriers of reduced-function CYP2C19 alleles are most susceptible to impairment of the anti-platelet effect of clopidogrel after concomitant PPI use. Individual subjects are not equally affected, and PPIs are not equally involved. However, large-scale randomized clinical trials are needed to evaluate the clinical outcome.
KEY WORDS
Clopidogrel • CYP2C19 polymorphism • Platelet aggregation • Proton pump inhibitors • TEG • VASP.
背景
CYP2C19基因多态性现象会影响氯吡格雷和质子泵抑制剂（PPI）的代谢。然而，同时使用这两种药物可能会降低预期的治疗效果。在本研究中，我们评估了携带不同数量功能降低的CYP2C19等位基因的个体是否受到同等影响，以及对CYP2C19代谢有不同依赖性的PPI是否同样参与其中。
方法
招募30名健康志愿者接受为期六周的氯吡格雷治疗方案。纳入三种对CYP2C19代谢有不同依赖性的PPI，并按此顺序分别给药。每种PPI给药一周，然后在下一种PPI干预前有一周的洗脱期。通过血栓弹力图血小板功能分析（TM）（TEG®）和血管扩张剂刺激磷蛋白（VASP）检测来检查抗血小板作用。
结果
TEG®和VASP检测均显示出相同的总体定性趋势，但TEG®检测到不同药物干预后血小板聚集有统计学意义的波动。TEG®结果还表明，非携带者在同时使用PPI后氯吡格雷的抗血小板作用受损最为显著。这种损害与PPI对CYP2C19的代谢依赖性密切相关。
结论
我们的研究表明，功能降低的CYP2C19等位基因非携带者在同时使用PPI后最易受到氯吡格雷抗血小板作用受损的影响。个体受试者受到的影响并不相同，PPI的参与情况也不尽相同。然而，需要大规模随机临床试验来评估临床结果。
关键词
氯吡格雷；CYP
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