PHARMACODYNAMICS AND PHARMACOKINETICS OF DMP-728, A PLATELET GPIIB IIIA ANTAGONIST, IN HEALTHY-SUBJECTS/

DMP 728 showed a dose-dependent inhibition of platelet aggregation at doses of 0.05 to 0.9 mg per subject, with a maximal inhibition (>90%) of platelet aggregation at doses of 0.9 mg per subject and higher. Min imal changes in bleeding time from baseline were observed at doses up to 0.6 mg per subject. At the 0.9 mg/subject dose level, bleeding time was prolonged by approximately twofold to threefold above the baselin e. At higher doses (1.5 mg/subject to 3.9 mg/subject), bleeding time p rolongation was >30 minutes during the infusion. In all dose groups, b leeding times returned to the control value within 8 hours after cessa tion of the infusion. Maximum plasma concentration and area under the curve of DMP 728 increased linearly and proportionally to the dose. No clinical changes in vital signs, 12-lead electrocardiograms, physical examinations, coagulation tests, or stool hemoccult tests were observ ed at any of the doses. In conclusion, DMP 728 is a potent antiplatele t agent and well tolerated at doses ranging from 0.05 to 3.0 mg/subjec t.