Effects of TAK-029, a novel GPIIb/IIIa antagonist, on arterial thrombosis in guinea pigs, dogs and monkeys.

The antithrombotic and bleeding time (BT) prolonging effects of TAK-029, a novel GPIIb/IIIa antagonist, were examined in three arterial thrombosis models. In guinea pigs, TAK-029 at 30 micrograms/kg (i.v.) inhibited ADP-induced ex vivo platelet aggregation completely and prolonged BT to 4.5 times the control value 5 min after administration, and it prevented thrombotic occlusion in 2 out of 5 animals in a photochemically-induced basilar thrombosis model. TAK-029 at 100 micrograms/kg (i.v.) prolonged BT more than 9 times 5 min after administration, and it prevented thrombus formation for over 60 min. In dogs, TAK-029 at 30 micrograms/kg (i.v.) inhibited ADP-induced ex vivo platelet aggregation by 87% 5 min after administration, and it prevented thrombotic occlusion in injured and stenosed coronary arteries for 22 min without prolonging the BT. TAK-029 at 100 micrograms/ kg (i.v.) inhibited platelet aggregation completely and prolonged BT 3.6 times 5 min after administration, and it prevented thrombus formation for over 45 min. In monkeys, TAK-029 at 10 micrograms/kg (i.v.) inhibited ADP-induced ex vivo platelet aggregation by 84% and prolonged BT 4.6 times 5 min after the administration, and it prevented thrombotic occlusion in injured and stenosed carotid arteries for 24 min. TAK-029 at 30 micrograms/kg (i.v.) completely inhibited platelet aggregation and thrombus formation for over 60 min, and it prolonged BT more than 7.3 times 60 min after administration. In conclusion, TAK-029 exerted potent antithrombotic effects with BT prolongation in three different arterial thrombosis models. TAK-029 may be effective for the treatment of various arterial thrombotic diseases.