Department of Pharmacology, Hamamatsu University School of Medicine, Hamamatsu-shi, Shizuoka, Japan.
Shin-nakagawa Hospital, Yokohama-shi, Kanagawa, Japan.
Clin Pharmacol Drug Dev. 2017 Jul;6(4):398-407. doi: 10.1002/cpdd.308. Epub 2016 Oct 26.
We evaluated the pharmacokinetics and pharmacodynamics of prasugrel used in combination with aspirin in healthy Japanese subjects. All subjects received aspirin 100 mg/day. Subsequently, in the single-administration study, 23 subjects also received prasugrel 20 or 30 mg, and in the multiple-administration study, 20 subjects received a loading dose of prasugrel 20 or 30 mg on day 1, followed by a maintenance dose of prasugrel 5 or 7.5 mg/day, respectively, on days 2-5. In both studies, the plasma concentration of the active metabolite of prasugrel, R-138727, reached a maximum 0.5 hours after administration and rapidly decreased within 4 hours. In the single-administration study, the inhibitory effect on adenosine diphosphate-induced platelet aggregation was significantly higher in the prasugrel 20- and 30-mg groups than in the placebo group at all times (1-144 hours) after administration. In the multiple-administration study, a similar antiplatelet effect was found after both the loading dose and the maintenance dose and was maintained for 3-6 days after the last administration. There were study drug-related adverse events; however, all were mild, and none was clinically significant.
我们评估了在健康日本受试者中联合使用阿司匹林的普拉格雷的药代动力学和药效学。所有受试者均每天接受 100mg 阿司匹林。随后,在单次给药研究中,23 名受试者还接受了 20 或 30mg 的普拉格雷,在多次给药研究中,20 名受试者在第 1 天接受了 20 或 30mg 的负荷剂量,随后在第 2-5 天分别接受 5 或 7.5mg/天的维持剂量。在两项研究中,普拉格雷的活性代谢物 R-138727 的血浆浓度在给药后 0.5 小时达到最大值,并在 4 小时内迅速下降。在单次给药研究中,与安慰剂组相比,在给药后 1-144 小时的所有时间点(1-144 小时),普拉格雷 20mg 和 30mg 组对二磷酸腺苷诱导的血小板聚集的抑制作用均显著更高。在多次给药研究中,在负荷剂量和维持剂量后均发现了类似的抗血小板作用,并且在最后一次给药后持续 3-6 天。存在与研究药物相关的不良事件;然而,所有这些都是轻微的,没有一个是临床上显著的。