Pickles H, Fish A, Hassan S, Burke C, Warrington S, O'Grady J
Clin Pharmacol Ther. 1983 Feb;33(2):178-82. doi: 10.1038/clpt.1983.27.
Normal subjects received infusions of epoprostenol (prostacyclin, PGI2) at doses of 2, 4, 6, and 8 ng/kg/min on each of two occasions after pretreatment with dipyridamole (400 mg/day for 3 days) or placebo. Baseline headache and bleeding time were increased and preejection period (PEP) shortened after dipyridamole. The baseline heart rate was increased on dipyridamole by an amount that correlated to the blood dipyridamole level. PGI2 infusion increased heart rate, systolic blood pressure (BP), pulse pressure, left ventricular ejection time index, and degree of flushing and severity of headache, and reduced diastolic BP, PEP, and T wave height. There was no apparent interaction between PGI2 and dipyridamole on these variables. PGI2 inhibited adenosine diphosphate-induced platelet aggregation and increased bleeding time. We conclude that, despite the synergism between dipyridamole and PGI2 that might be predicted and has been demonstrated in some animal experiments, no such interaction is apparent in normal humans after standard doses.
正常受试者在接受双嘧达莫(400mg/天,共3天)或安慰剂预处理后的两个不同时间,分别以2、4、6和8 ng/kg/分钟的剂量输注依前列醇(前列环素,PGI2)。双嘧达莫治疗后,基线头痛和出血时间增加,射血前期(PEP)缩短。双嘧达莫使基线心率增加,且增加幅度与血液中双嘧达莫水平相关。输注PGI2可使心率、收缩压(BP)、脉压、左心室射血时间指数、潮红程度和头痛严重程度增加,使舒张压、PEP和T波高度降低。在这些变量上,PGI2和双嘧达莫之间没有明显的相互作用。PGI2抑制二磷酸腺苷诱导的血小板聚集并延长出血时间。我们得出结论,尽管双嘧达莫和PGI2之间可能存在协同作用,且在一些动物实验中已得到证实,但在正常人类中,标准剂量下并未出现这种相互作用。