Herbert J M, Laplace M C, Maffrand J P
Haemobiology Research Department Sanofi Recherche, Toulouse, France.
J Lipid Mediat. 1992 Feb;5(1):1-12.
Pharmacodynamics of SR 27417, a novel, specific platelet-activating factor (PAF) antagonist was monitored with ex vivo PAF-induced platelet aggregation in the rabbit. Single per os administration of SR 27417 (5 mg/kg) resulted in complete inhibition of this aggregation for at least 3 days. The magnitude of this inhibitory effect was dose-dependent with a maximum effect 1-3 h after oral administration. IC50 values for PAF-induced platelet aggregation were 80, 35, 50 and 1250 micrograms/kg, 1, 3, 24 and 72 h after oral intake of SR 27417 respectively. This effect was irreversible in nature since it could not be overcome by prolonged incubation of platelets isolated from treated animals in plasma from controls or in buffer. Examination of [3H]-PAF binding to washed platelets isolated 5 min after i.v. administration of increasing concentrations of SR 27417 revealed a competitive-type of inhibition whereas 24 h after p.o. administration, SR 27417 antagonized [3H]-PAF binding in a non-competitive manner.
采用兔体内血小板激活因子（PAF）诱导的血小板聚集实验监测了新型特异性PAF拮抗剂SR 27417的药效学。单次口服给予SR 27417（5mg/kg）可导致该聚集被完全抑制至少3天。这种抑制作用的强度呈剂量依赖性，口服给药后1 - 3小时达到最大效应。口服SR 27417后1、3、24和72小时，PAF诱导的血小板聚集的IC50值分别为80、35、50和1250微克/千克。由于从处理过的动物分离的血小板在对照血浆或缓冲液中长时间孵育无法克服这种作用，所以这种效应本质上是不可逆的。静脉注射不同浓度的SR 27417 5分钟后，对分离的洗涤血小板进行[3H]-PAF结合检测，结果显示为竞争性抑制类型；而口服给药24小时后，SR 27417以非竞争性方式拮抗[3H]-PAF结合。
