Mallikaarjun S, Forbes W P, Bramer S L
Department of Clinical Pharmacokinetics/Pharmacodynamics & Metabolism, Otsuka America Pharmaceutical, Inc., Rockville, MD 20850, USA.
Clin Pharmacokinet. 1999;37 Suppl 2:87-93. doi: 10.2165/00003088-199937002-00010.
This study evaluated the effects of repeated oral drug administration with cilostazol alone and with aspirin (acetylsalicylic acid) on platelet aggregation, coagulation and bleeding time as well as the cilostazol-aspirin pharmacokinetic interaction in healthy males.
This was a randomised, double-blind, placebo-controlled, crossover study. Participants received either cilostazol 100 mg or placebo twice a day for 10 days; aspirin 325 mg/day was coadministered for the last 5 days. After a 14-day washout period, participants received the alternative treatment.
12 healthy male volunteers were enrolled.
Differences in bleeding times, platelet aggregation, prothrombin time (PT) and activated partial thromboplastin time (aPTT) between cilostazol with aspirin and cilostazol alone. Noncompartmental pharmacokinetic parameters were determined for each study participant.
Cilostazol, with or without aspirin, caused no changes in PT, aPTT or bleeding time. There was a 23 to 35% increase in inhibition of ADP-induced ex vivo platelet aggregation by cilostazol plus aspirin when compared with aspirin alone. There was no additive or synergistic effect on arachidonic acid-induced platelet aggregation. Statistically significant but clinically insignificant increases in the area under the plasma concentration-time curve to the last measurable plasma concentration and trough concentrations of cilostazol and its metabolites (OPC-13015 and OPC-13213) occurred after aspirin coadministration, with no differences observed in the maximum plasma concentration Drug-related adverse events were generally mild, the most frequent being headache.
Cilostazol and aspirin coadministration did not cause clinically significant changes in PT, aPTT, bleeding time, platelet aggregation or plasma concentrations of cilostazol and its 2 active metabolites. Cilostazol was generally well tolerated with or without aspirin.
本研究评估了在健康男性中单独口服西洛他唑以及与阿司匹林（乙酰水杨酸）联合重复给药对血小板聚集、凝血和出血时间的影响，以及西洛他唑 - 阿司匹林的药代动力学相互作用。
这是一项随机、双盲、安慰剂对照的交叉研究。参与者每天两次接受西洛他唑100毫克或安慰剂，共10天；在最后5天同时给予阿司匹林325毫克/天。经过14天的洗脱期后，参与者接受替代治疗。
招募了12名健康男性志愿者。
西洛他唑与阿司匹林联合使用和单独使用西洛他唑时出血时间、血小板聚集、凝血酶原时间（PT）和活化部分凝血活酶时间（aPTT）的差异。为每位研究参与者测定非房室药代动力学参数。
无论是否与阿司匹林联合，西洛他唑均未引起PT、aPTT或出血时间的变化。与单独使用阿司匹林相比，西洛他唑加阿司匹林对ADP诱导的体外血小板聚集的抑制作用增加了23%至35%。对花生四烯酸诱导的血小板聚集没有相加或协同作用。在联合使用阿司匹林后，西洛他唑及其代谢产物（OPC - 13015和OPC - 13213）的血浆浓度 - 时间曲线下面积至最后可测量血浆浓度和谷浓度出现统计学上显著但临床上无显著意义的增加，最大血浆浓度未见差异。与药物相关的不良事件一般较轻，最常见的是头痛。
西洛他唑与阿司匹林联合使用在PT、aPTT、出血时间、血小板聚集或西洛他唑及其两种活性代谢产物的血浆浓度方面未引起临床上显著的变化。无论是否与阿司匹林联合，西洛他唑总体耐受性良好。
