Fujimura A, Shiga T, Kumagai Y, Ohashi K, Ebihara A, Kotegawa T
Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan.
J Clin Pharmacol. 1996 May;36(5):409-13. doi: 10.1002/j.1552-4604.1996.tb05027.x.
To study the pharmacokinetics of a new thromboxane A2 (TXA2) receptor antagonist, S-1452, eight healthy volunteers were given placebo or S-1452 orally on four occasions in step-wise increasing doses of 10 mg, 25 mg, and 50 mg separated by 2-week intervals. Blood samples for measurement of plasma concentrations of the drug and of its inhibitory effect on platelet aggregation were obtained for 24 hours after administration. Bleeding time after administration was measured. S-1452 was rapidly absorbed, with a peak plasma concentration at 30 minutes after administration. Thereafter, the drug was rapidly eliminated (elimination half-life, 0.4-0.5 hours), and no drug was detected at 6 hours. The inhibitory effect of S-1452 on platelet aggregation, which was stimulated by the TXA2 receptor agonist U-46619, persisted more than 6 hours after drug administration. Bleeding time was slightly prolonged after a single dose of S-1452. These results suggest that although S-1452 is rapidly eliminated in plasma, its inhibitory effects on platelet aggregation persist for a longer period. Careful observations are needed to prevent potential bleeding episodes during repeated treatment with the drug.
为研究新型血栓素A2（TXA2）受体拮抗剂S - 1452的药代动力学，8名健康志愿者分4次口服安慰剂或S - 1452，剂量逐步递增，依次为10毫克、25毫克和50毫克，每次间隔2周。给药后24小时采集血样，测定药物的血浆浓度及其对血小板聚集的抑制作用。测定给药后的出血时间。S - 1452吸收迅速，给药后30分钟达到血浆峰浓度。此后，药物迅速消除（消除半衰期为0.4 - 0.5小时），6小时后未检测到药物。S - 1452对TXA2受体激动剂U - 46619刺激的血小板聚集的抑制作用在给药后持续超过6小时。单次服用S - 1452后出血时间略有延长。这些结果表明，尽管S - 1452在血浆中迅速消除，但其对血小板聚集的抑制作用持续较长时间。在该药物重复治疗期间，需要仔细观察以预防潜在的出血事件。
