Effect of CV-4151 (Isbogrel), a Thromboxane A2 Synthase Inhibitor, on Bleeding Time in Rats:Combined Effect with Antiplatelet, Anticoagulant and Thrombolytic Agents
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Effect of CV-4151, a thromboxane A2 synthase inhibitor, on antithrombotic and thrombolytic agents-induced bleeding time prolongation was examined in rats. CV-4151, ticlopidine, ozagrel and warfarin singly at doses greater than 0.3, 300, 1 and 0.5mg/kg, p. o. respectively, significantly prolonged bleeding time. Aspirin (10mg/kg, p. o.) also prolonged bleeding time. Tissue-type plasminogen activator (TPA, 2×104 IU/kg/min i. v. infusion) and urokinase (UK, 4×104IU/kg/min i. v. infusion) showed significant prolongation of bleeding time. Prologing effect of CV-4151 on bleeding time was weaker than those of warfarin and thrombolytic agents.In combined experiments with CV-4151 and other agents, CV-4151 moderately enhanced ticlopidine-induced bleeding time prolongation, and markedly enhanced warfarin-, TPA-and UK-induced bleeding time prolongation. On the other hand, CV-4151 had no effect on aspirin-induced bleeding time prolongation.Thus, CV-4151 markedly enhanced bleeding time prolongation caused by an oral anticoagulant and thrombolytic agents in rats.
- 一般社団法人 日本血栓止血学会の論文
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