Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
Department of Neurology, Seoul National University Hospital, Seoul, Korea.
Clin Pharmacol Ther. 2014 Jun;95(6):608-16. doi: 10.1038/clpt.2014.49. Epub 2014 Feb 24.
Decreased oral clopidogrel absorption caused by induction of intestinal permeability glycoprotein (P-gp) expression after aspirin administration was observed in rats. This study evaluated the effect of aspirin coadministration on the pharmacokinetics/pharmacodynamics of clopidogrel in humans. A single 75-mg dose of clopidogrel was orally administered before and after 2 and 4 weeks of once-daily 100-mg aspirin administration in 18 healthy volunteers who were recruited based on CYP2C19 and PON1 genotypes. Plasma concentrations of clopidogrel and its active metabolite, H4, and relative platelet inhibition (RPI) were determined. The P-gp microRNA miR-27a increased by up to 7.67-fold (P = 0.004) and the clopidogrel area under the concentration-time curve (AUC) decreased by 14% (P > 0.05), but the AUC of H4 remained unchanged and RPI increased by up to 15% (P = 0.002) after aspirin administration. These findings indicate low-dose aspirin coadministration may decrease clopidogrel bioavailability but does not decrease its efficacy.
阿司匹林给药后诱导肠道通透性糖蛋白（P-gp）表达，导致口服氯吡格雷吸收减少，在大鼠中观察到。本研究评估了阿司匹林合用对健康志愿者氯吡格雷药代动力学/药效学的影响。18 名健康志愿者根据 CYP2C19 和 PON1 基因型，每天口服 100mg 阿司匹林 2 周和 4 周后，分别单次口服 75mg 氯吡格雷，并进行了研究。测定了氯吡格雷及其活性代谢物 H4 的血浆浓度和相对血小板抑制率（RPI）。P-gp 微 RNA miR-27a 增加了 7.67 倍（P=0.004），氯吡格雷浓度-时间曲线下面积（AUC）减少了 14%（P>0.05），但 H4 的 AUC 保持不变，RPI 增加了 15%（P=0.002）。这些发现表明，小剂量阿司匹林合用可能会降低氯吡格雷的生物利用度，但不会降低其疗效。
