COMPARISON OF THE ANTIPLATELET EFFECT OF YM337 AND ABCIXIMAB IN RHESUS-MONKEYS

We directly compared the effects of YM337, the Fab fragment of the hum anized monoclonal antibody C4G1, on platelet aggregation and template bleeding time with those of abciximab, the Fab fragment of the human/m urine chimeric monoclonal antibody 7E3, in rhesus monkeys. The duratio n of inhibition of platelet aggregation by abciximab after i.v. bolus injection was much longer than that by YM337. Although YM337 significa ntly prolonged template bleeding time at 5 min after i.v. bolus inject ion, this action recovered within 1 h after injection. In contrast, al though abciximab also prolonged template bleeding time, the duration o f this effect was sustained. In a dose-escalating continuous infusion study, we evaluated the relationship between inhibition of platelet ag gregation and prolongation of template bleeding time. Platelet aggrega tion was inhibited by over 80% by both agents at 3 mu g/kg per min, an d template bleeding time was prolonged to about 30 min at 30 mu g/kg p er min for YM337 and 10 mu g/kg per min for abciximab. Interestingly, plasma concentrations between inhibition of platelet aggregation and p rolongation of template bleeding time did not overlap with YM337, but did overlap with abciximab. These results suggest that YM337 allows ea sier control of antiplatelet activity with less effect on bleeding tim e than abciximab, and has a wider therapeutic window than abciximab. ( C) 1997 Elsevier Science B.V.