Effects of the proton pump inhibitor lansoprazole on the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel
Effects of the proton pump inhibitor lansoprazole on the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel
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DOI：
10.1177/0091270008315310
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发表时间：
2008-04-01
影响因子：
2.9
通讯作者：
Winters, Kenneth J.
中科院分区：
文献类型：
--
作者：
Small, David S.;Farid, Nagy A.;Winters, Kenneth J.
普罗格雷和氯吡格雷是硫代吡啶前体药物，它们各自被代谢成一种抑制血小板P2Y(12)ADP受体的活性代谢物。在这项开放的4期交叉研究中，我们评价了质子泵抑制剂兰索拉唑对单剂量服用普拉格雷60 mg和氯吡格雷300 mg并与兰索拉唑30 mg/d同时服药的健康受试者普拉格雷和氯吡格雷的药代动力学和药效学的影响。测定了普拉格雷活性代谢物R-138727和氯吡格雷非活性羧酸代谢物SR26334的C-max和AUC(0-tlast)。在每次治疗后4~24小时用比浊法测定血小板聚集抑制(IPA)。兰索拉唑(1)给药后，R-138727 AUC(0-tlast)和C-max分别降低13%和29%，但对IPA无影响；一项回顾性的三联分析显示，在单独服用氯吡格雷后IPA升高的受试者中，兰索拉唑降低了IPA，而在相同剂量的受试者中，服用普拉格雷后IPA没有受到影响。总体数据表明，在服用普拉格雷和质子泵抑制剂(如兰索拉唑)的个体中，普拉格雷的剂量调整不太可能是合理的。
Prosugrel and clopidogrel, thienopydine prodrugs, are each metabolized to an active metabolite that inhibits the platelet P2Y(12) ADP receptor. In this open-label, 4-period crossover study, the effects of the proton pump inhibitor lansoprazole on the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel were assessed in healthy subjects given single doses of prasugrel 60 mg and clopidogrel 300 mg with and without concurrent lansoprazole 30 mg qd. C-max and AUC(0-tlast) of prasugrel's active metabolite, R-138727, and clopidogrel's inactive carboxylic acid metabolite, SR26334, were assessed. Inhibition of platelet aggregation (IPA) was measured by turbidimetric aggregometry 4 to 24 hours after each treatment. Lansoprazole (1) decreased R-138727 AUC(0-tlast) and C-max by 13% and 29%, respectively, but did not affect IPA after the prasugrel dose, and (2) did not affect SR62334 exposure but tended to lower IPA after a clopidogrel dose. A retrospective tertile analysis showed in subjects with high IPA after a clopidogrel dose alone that lansoprazole decreased IPA, whereas IPA was unaffected in these same subjects after a prasugrel dose. The overall data suggest that a prasugrel dose adjustment is not likely warranted in an individual taking prasugrel with a proton pump inhibitor such as lansoprazole.