Fujitani K, Kambayashi J, Murata K, Yano Y, Shinozaki K, Yukawa M, Sakon M, Murata T, Kawasaki T, Shiba E
Department of Surgery II, Osaka University Medical School, Japan.
Pharmacol Res. 1995 Feb;31(2):121-5. doi: 10.1016/1043-6618(95)80057-3.
Among various oral antiplatelets, a combination of a novel prostacyclin analogue beraprost (BPT) and a potent phosphodiesterase inhibitor cilostazol (CLZ) may result in untoward clinical effects due to possible synergistic elevation of intracellular cAMP (cyclic adenosine 3',5'-monophosphate). Thereby, a clinical study of the combined administration of the two agents was attempted. Twelve healthy volunteers were assigned to take BPT/CLZ in the following schedule; BPT: 40 micrograms at day 1 and 120 micrograms t.i.d. from day 7 to 14, CLZ: 200 mg t.i.d. from day 3 to 14. At various time intervals, physical examination and blood collection for ex vivo platelet aggregation and determination of intraplatelet cAMP were performed. Throughout the observation period, no significant alteration in vital signs was observed. Seven out of 12 subjects experienced headache of a short duration accompanying facial flush in one and nausea in one, especially after ingestion of CLZ. All of these symptoms, probably caused by the vasodilating effect of the two agents, were of mild degree and no special treatment was required. Intraplatelet cAMP content was gradually but significantly increased to 9.84 +/- 4.59 pmol per 10(9) platelets at day 14 in comparison with the initial value (6.87 +/- 2.25 pmol). The platelet aggregability was significantly suppressed at various time intervals but no additive or synergistic inhibitory effect by the combined administration was noted. In conclusion, the combined administration of BPT/CLZ is safe at doses used in the study, though the beneficial clinical effect of the combined administration has yet to be elucidated.
在各种口服抗血小板药物中，新型前列环素类似物贝拉前列素（BPT）与强效磷酸二酯酶抑制剂西洛他唑（CLZ）联合使用可能会因细胞内环磷酸腺苷（cAMP）水平可能的协同升高而产生不良临床效应。因此，尝试开展一项关于这两种药物联合给药的临床研究。12名健康志愿者按照以下方案服用BPT/CLZ；BPT：第1天服用40微克，从第7天至第14天每天三次，每次120微克；CLZ：从第3天至第14天每天三次，每次200毫克。在不同时间间隔进行体格检查，并采集血液用于体外血小板聚集检测及血小板内cAMP测定。在整个观察期内，生命体征未观察到明显变化。12名受试者中有7名经历了短暂头痛，其中1名伴有面部潮红，1名伴有恶心，尤其是在服用CLZ后。所有这些症状可能是由这两种药物的血管舒张作用引起的，程度较轻，无需特殊治疗。与初始值（6.87±2.25皮摩尔）相比，血小板内cAMP含量在第14天逐渐但显著增加至每10⁹个血小板9.84±4.59皮摩尔。血小板聚集性在不同时间间隔均受到显著抑制，但联合给药未观察到相加或协同抑制作用。总之，在本研究使用的剂量下，BPT/CLZ联合给药是安全的，尽管联合给药的有益临床效果尚待阐明。
