Oral antiplatelet efficacy of the platelet GPIIb/IIIa antagonist, DMP754 in non-human primates

Binding kinetic studies with XV459, the active form of DMP754, demonstrated comparable binding kinetics (Kd and Koff) with platelets obtained from either human or baboons which were different from that with platelets obtained from dogs. Therefore, the present study was undertaken to evaluate the antiplatelet efficacy of DMP754 following oral administration 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 DMP754 resulted in dose- and time-related inhibition of platelet aggregation 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 maximal antiplatelet doses DMP754 demonstrated no significant effects on platelet count, clinical chemistry or hemodynamic profiles in baboons. These data suggest that DMP754 is a potent orally active antiplatelet agent with extended duration after once a day oral administration in non-human primate.