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. Minimal 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 baseline. At higher doses (1.5 mg/subject to 3.9 mg/subject), bleeding time prolongation was > 30 minutes during the infusion. In all dose groups, bleeding times returned to the control value within 8 hours after cessation 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 observed at any of the doses. In conclusion, DMP 728 is a potent antiplatelet agent and well tolerated at doses ranging from 0.05 to 3.0 mg/subject.
Michaelis
W
W
DuPont Merck Pharmaceutical Co., Wilmington, DE 19880, USA.
Turlapaty
P
P
Gray
J
J
Fiske
W D
WD
Faulkner
E
E
Kornhauser
D
D
Mousa
S A
SA
D000328:Adult; D001760:Bleeding Time; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008698:Mesylates / Q000493:pharmacokinetics / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000493:pharmacokinetics / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D012016:Reference Values
D008698:Mesylates; D010456:Peptides, Cyclic; D010975:Platelet Aggregation Inhibitors; C085286:DMP 728