University of Florida College of Medicine-Jacksonville, Jacksonville, FL 32209, USA.
Circ Cardiovasc Interv. 2010 Oct;3(5):436-41. doi: 10.1161/CIRCINTERVENTIONS.110.957829. Epub 2010 Sep 21.
A drug interaction between clopidogrel and omeprazole resulting in impaired platelet inhibition has been reported. It has been suggested that staggering administration of clopidogrel and omeprazole may overcome this pharmacodynamic (PD) interaction.
This prospective, open-label, 3-period, randomized crossover study was performed in 20 healthy volunteers. Subjects were randomly selected to receive omeprazole (40 mg daily) concomitantly (CONC) or staggered by 8 to 12 hours (STAG) for 1 week on a background of clopidogrel therapy in a crossover fashion, with a 2- to 4-week washout period between treatments. After another 2- to 4-week washout period, all subjects were treated for 1 week with clopidogrel alone. Clopidogrel was administered as a 600-mg loading dose followed by a 75-mg maintenance dose during all phases. PD effects were assessed by vasodilator-stimulated phosphoprotein phosphorylation assay, VerifyNow P2Y(12) system, and light transmittance aggregometry at baseline, 24 hours, and 1 week. The primary end point was the comparison of P2Y(12) reactivity index assessed by vasodilator-stimulated phosphoprotein phosphorylation assay at 1 week between CONC and STAG regimens. No significant difference in the primary end point was observed (least squares mean ± SEM, 56.1 ± 3.5% for CONC versus 61.6 ± 3.4% for STAG; P = 0.08). P2Y(12) reactivity index values were significantly lower in the clopidogrel regimen (48.8 ±3.4%) than in the CONC (P = 0.02) and STAG (P = 0.001) regimens. No PD differences were observed between regimens at baseline and 24 hours. Concordant results were obtained by P2Y(12)-specific assessments using VerifyNow but not with light transmittance aggregometry.
Omeprazole impairs clopidogrel-induced antiplatelet effects in the maintenance phase of treatment irrespective of timing of their administration.
已有报道称氯吡格雷与奥美拉唑之间存在药物相互作用，导致血小板抑制作用受损。有研究表明，错开氯吡格雷和奥美拉唑的给药时间可能会克服这种药效学（PD）相互作用。
这是一项前瞻性、开放标签、3 期、随机交叉研究，在 20 名健康志愿者中进行。受试者随机选择接受奥美拉唑（每日 40 毫克）同时（CONC）或错开 8 至 12 小时（STAG）给药，在交叉方式下接受氯吡格雷治疗 1 周，两种治疗之间有 2 至 4 周的洗脱期。在另一个 2 至 4 周的洗脱期后，所有受试者单独接受氯吡格雷治疗 1 周。在所有阶段，氯吡格雷均给予 600 毫克负荷剂量，随后给予 75 毫克维持剂量。PD 效应通过血管扩张刺激磷酸蛋白磷酸化测定、VerifyNow P2Y(12)系统和光透射聚集度测定在基线、24 小时和 1 周时进行评估。主要终点是比较血管扩张刺激磷酸蛋白磷酸化测定在 1 周时的 P2Y(12)反应指数，CONC 和 STAG 方案之间的比较。主要终点没有观察到显著差异（最小二乘均数±SEM，CONC 为 56.1±3.5%，STAG 为 61.6±3.4%；P=0.08）。氯吡格雷方案的 P2Y(12)反应指数值明显低于 CONC（P=0.02）和 STAG（P=0.001）方案（48.8±3.4%）。在基线和 24 小时时，方案之间没有观察到 PD 差异。使用 VerifyNow 进行的 P2Y(12)-特异性评估获得了一致的结果，但使用光透射聚集度测定则没有。
奥美拉唑在治疗的维持阶段会损害氯吡格雷诱导的抗血小板作用，而与给药时间无关。
