Adamus W S, Heuer H, Meade C J
Department of Medicine (Human Pharmacology Centre), Boehringer Ingelheim KG, Ingelheim/Rhein, Federal Republic of Germany.
Methods Find Exp Clin Pharmacol. 1989 Jun;11(6):415-20.
Platelet aggregation induced ex vivo by aggregating factors such as adrenaline, ADP, collagen or PAF may be useful as a model for describing drug effects in humans. In the two studies reported here, PAF-induced platelet aggregation ex vivo was used as an indicator of the pharmacological activity in healthy volunteers of the newly developed specific PAF-antagonist WEB 2086. In intravenous and inhalative single rising dose tolerance trials this method proved useful for monitoring the pharmacological action of the compound tested. After administration of placebo no relevant pharmacological activity was observed. In both studies increasing dosages of the test substance showed clear, dose-related inhibition of PAF-induced platelet aggregation. Ex vivo PAF-induced platelet aggregation thus provides a simple and rapid means of assessing functional PAF antagonism during trials of PAF-antagonists in human volunteers.
由肾上腺素、二磷酸腺苷（ADP）、胶原蛋白或血小板激活因子（PAF）等聚集因子在体外诱导的血小板聚集，可作为描述药物对人体作用的模型。在本文报道的两项研究中，体外PAF诱导的血小板聚集被用作新开发的特异性PAF拮抗剂WEB 2086在健康志愿者体内药理活性的指标。在静脉注射和吸入单次递增剂量耐受性试验中，该方法被证明可用于监测受试化合物的药理作用。给予安慰剂后，未观察到相关药理活性。在两项研究中，受试物质剂量增加均显示出对PAF诱导的血小板聚集有明显的、剂量相关的抑制作用。因此，体外PAF诱导的血小板聚集为在人类志愿者中进行PAF拮抗剂试验期间评估功能性PAF拮抗作用提供了一种简单快速的方法。
