ANTITHROMBOTIC EFFECTS OF KBT-3022, A NOVEL ANTIPLATELET AGENT, IN ANARTERIAL THROMBOSIS MODEL IN THE GUINEA-PIG

We examined the antithrombotic effect of KBT-3022, a novel antiplatele t 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 mu mole) , 0.3 mg (0.7 mu mole), 1 mg (2.2 mu mole) and 3 mg (6.7 mu mole)/kg, p.o.] 3 h prior to thrombosis induction prolonged the time required to achieve the thrombotic occlusion and inhibited the collagen (low conc entration, 0.2 mu g/ml; high concentration, 1 mu g/ml)-induced platele t aggregation in whole blood ex vivo, each effect being concentration- dependent. The effects were tested of ticlopidine [30 mg (99.9 mu mole ), 100 mg (333.1 mu mole) and 300 mg (999.2 mu mole)/kg, p.o.] and asp irin [10 mg (55.5 mu mole), 30 mg (166.5 mu mole) and 100 mg (555.1 mu mole)/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. A spirin [100 mg (555.1 mu mole)/kg, p.o.], bur not ticlopidine (at any concentration), inhibited the collagen (high concentration)-induced pl atelet aggregation. A good correlation was found between the antithrom botic and antiplateler-aggregating effects of both KBT-3022 and aspiri n, but not of ticlopidine. The antithrombotic potency of KBT-3022 was 300 times that of aspirin and 1000 times that of ticlopidine. These ob servations suggest that KBT-3022 may be clinically effective against p latelet-rich thrombosis. Drug Dev. Res. 40:217-222, 1997. (C) 1997 Wil ey-Liss, Inc.