Table2_Effects of ilaprazole on the steady-state pharmacodynamics of clopidogrel in healthy volunteers: An open-label randomized crossover study.DOCX

Background: Previous studies have suggested that proton pump inhibitors could impair the antiplatelet effect of clopidogrel. It is uncertain whether ilaprazole affects the antiplatelet effect of clopidogrel. This study aimed to determine the drug-drug interaction between ilaprazole and clopidogrel.
Methods: A randomized crossover trial of 40 healthy subjects was performed. Clopidogrel was administered alone or in combination with ilaprazole for 7 days. The maximal platelet aggregation (MPA) to 5 μmol/L adenosine diphosphate was measured by light transmission aggregometry and the platelet reactivity index (PRI) was determined by vasodilator-stimulated phosphoprotein P2Y12 assay. High on-treatment platelet reactivity (HOPR) was defined as a MPA of >40%. The inhibition of platelet aggregation (IPA) and PRI in the two phases were compared between two regimens after the last dosing.
Results: IPA was comparable between the two regimens at 0, 10 and 24 h (p > 0.05), but higher at 4 h in the clopidogrel alone regimen compared with that in the combined treatment regimen (75.66 ± 18.44% vs. 70.18 ± 17.67%, p = 0.031). The inhibition of PRI was comparable between the two regimens at 0 and 24 h. There were no significant differences in the area under the time-IPA% curve (AUC) or the incidence of HOPR at all time-points between the two regimens.
Conclusion: In healthy subjects, ilaprazole has limited effect on the pharmacodynamics of clopidogrel and it may not be clinically relevant.
Clinical Trial Registration: [www.chictr.org.cn], identifier [ChiCTR2000031482].

背景：既往研究提示，质子泵抑制剂（proton pump inhibitors）可能削弱氯吡格雷（clopidogrel）的抗血小板作用。目前尚不明确艾普拉唑（ilaprazole）是否会影响氯吡格雷的抗血小板效应。本研究旨在明确艾普拉唑与氯吡格雷之间的药物相互作用。
方法：本研究纳入40名健康受试者，开展随机交叉试验。受试者分别单用氯吡格雷，或联合艾普拉唑给药，持续7天。采用光透射聚集法检测5μmol/L二磷酸腺苷（adenosine diphosphate）诱导的最大血小板聚集率（maximal platelet aggregation, MPA），并通过血管扩张刺激磷蛋白P2Y12检测法测定血小板反应指数（platelet reactivity index, PRI）。将治疗时高血小板反应性（high on-treatment platelet reactivity, HOPR）定义为MPA＞40%。末次给药后，比较两种给药方案下两个阶段的血小板聚集抑制率（inhibition of platelet aggregation, IPA）与PRI。
结果：给药后0、10和24h，两种方案的IPA水平相当（p＞0.05）；但给药后4h，单用氯吡格雷组的IPA水平高于联合给药组（75.66±18.44% vs. 70.18±17.67%，p=0.031）。PRI抑制率在给药后0和24h时两种方案无显著差异。两种方案的时间-IPA%曲线下面积（area under the time-IPA% curve, AUC）以及各时间点的HOPR发生率均无显著差异。
结论：在健康受试者中，艾普拉唑对氯吡格雷的药效学影响有限，临床相关性可能较低。
临床试验注册：[www.chictr.org.cn]，注册号[ChiCTR2000031482]。