COMPARISON OF THE ANTITHROMBOTIC EFFECTS OF FK633, GPIIB IIIA ANTAGONIST, AND ASPIRIN IN A GUINEA-PIG THROMBOSIS MODEL/

Antiplatelet and antithrombotic effects of FK633 (a GPIIb/IIIa antagon ist) and aspirin were compared. FK633 at 0.32 mg/kg i,v, or aspirin at 10 mg/kg i.v. inhibited ex vivo collagen-induced aggregation by >50% for 1 hour in guinea pigs. However, aspirin was very weak in inhibitin g ADP-induced aggregation. In vivo antithrombotic effects of FK633 and aspirin were compared using a FeCl3-induced carotid artery thrombosis model in guinea pigs. Pretreatment with 0.32 mg/kg i.v. of FK633 sign ificantly prevented occlusive thrombus formation, but aspirin at 10 mg /kg i.v, did not. In thrombolysis experiments, adjunctive use of FK633 (0.32 mg/kg i.v.) with rt-PA (0.3 mg/kg bolus+1.0 mg/kg/hr) achieved reperfusion in five of five animals without reocclusion. Aspirin (10 m g/kg i.v.) with rt-PA also achieved reperfusion in three of five anima ls with high incidence of reocclusion. These results suggest that FK63 3 may be a more effective antithrombotic agent than aspirin due to its agonist-independent antiplatelet effects. (C) 1998 Elsevier Science L td.