ORAL ANTIPLATELET EFFICACY OF THE PLATELET GPIIB IIIA ANTAGONIST, DMP754 IN NONHUMAN-PRIMATES/

Binding kinetic studies with XV459, the active form of DMP754, demonst rated comparable binding kinetics (Kd and Koff) with platelets obtaine d from either human or baboons which were different from that with pla telets obtained from dogs. Therefore, the present study was undertaken to evaluate the antiplatelet efficacy of DMP754 following oral admini stration in baboons. The dose levels evaluated were 0.1 and 1.0 mg/kg, IV and 0.1, 0.3, 1.0, and 3.0 mg/kg, oral of DMP754. Oral doses of DM P754 resulted in dose-and time-related inhibition of platelet aggregat ion along with a modest effect on bleeding time prolongation DMP754 at similar oral doses had 24 hours of antiplatelet effects in baboon as compared to 8-12 hours duration of antiplatelet efficacy in dogs. At m aximal antiplatelet doses DMP754 demonstrated no significant effects o n platelet count, clinical chemistry or hemodynamic profiles in baboon s. These data suggest that DMP754 is a potent orally active antiplatel et agent with extended duration after once a day oral administration i n non-human primate. (C) 1998 DuPont Merck Pharmaceutical Company. Pub lished by Elsevier Science Ltd.