Antithrombotic effects of KBT-3022, a novel antiplatelet agent,in an arterial thrombosis model in the guinea-pig

We examined the antithrombotic effect of KBT-3022, a novel antiplatelet agent, on photochemically induced arterial thrombosis in the guinea-pig saphenous artery, and compared its effect with that of aspirin and that of ticlopidine. Pretreatment with KBT-3022 [0.1 mg (0.2 μmole), 0.3 mg (0.7 μmole), 1 mg (2.2 μmole) and 3 mg (6.7 μmole)/kg, p.o.] 3 h prior to thrombosis induction prolonged the time required to achieve the thrombotic occlusion and inhibited the collagen (low concentration, 0.2 μg/ml; high concentration, 1 μg/ml)-induced platelet aggregation in whole blood ex vivo, each effect being concentration-dependent. The effects were tested of ticlopidine [30 mg (99.9 μmole), 100 mg (333.1 μmole) and 300 mg (999.2 μmole)/kg, p.o.] and aspirin [10 mg (55.5 μmole), 30 mg (166.5 μmole) and 100 mg (555.1 μmole)/kg, p.o.]. Both drugs prolonged the time to occlusion (but only at their highest concentration), and also inhibited the collagen (low concentration)- induced platelet aggregation in whole blood ex vivo. Aspirin [100 mg (555.1 μmole)/kg, p.o.], but not ticlopidine (at any concentration), inhibited the collagen (high concentration)-induced platelet aggregation. A good correlation was found between the antithrombotic and antiplatelet-aggregating effects of both KBT-3022 and aspirin, but not of ticlopidine. The antithrombotic potency of KBT-3022 was 300 times that of aspirin and 1000 times that of ticlopidine. These observations suggest that KBT-3022 may be clinically effective against platelet-rich thrombosis. Drug Dev. Res. 40:217–222, 1997. © 1997 Wiley-Liss, Inc.