Antiplatelet effects of MK-852, a platelet fibrinogen receptor antagonist, in healthy volunteers

J Clin Pharmacol. 2000 May;40(5):496-507. doi: 10.1177/00912700022009116.

Abstract

MK-852, a cyclic heptapeptide, is a potent platelet fibrinogen receptor antagonist. When administered to normal healthy male subjects by 1- and 4-hour constant rate intravenous infusions, it provides a generally well-tolerated and reversible means of inhibition of platelet function. At infusion rates of 1 microgram/kg/min for 1 hour and 0.44 microgram/kg/min for 4 hours, respectively, MK-852 extended baseline bleeding time by greater than 2.2-fold and 2.6-fold, inhibited ADP-induced platelet aggregation by 76% and 69%, and inhibited collagen-induced platelet aggregation by 65% and 67%, respectively. The pharmacokinetics of MK-852 include an elimination half-life of approximately 2 hours, total clearance of about 150 ml/min, and volume of distribution of about 18 liters. Examination of the relationship between MK-852 whole-blood concentration in vitro and inhibition of platelet aggregation showed an EC50 of about 55 ng/ml and a Hill coefficient of 1.55. The infusions were generally well tolerated, with no study drug-related changes in blood counts or biochemical profiles.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adenosine Diphosphate / pharmacology
  • Adult
  • Area Under Curve
  • Collagen / pharmacology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Humans
  • Infusions, Intravenous
  • Male
  • Metabolic Clearance Rate
  • Oligopeptides / blood
  • Oligopeptides / pharmacokinetics
  • Oligopeptides / pharmacology*
  • Peptides, Cyclic / blood
  • Peptides, Cyclic / pharmacokinetics
  • Peptides, Cyclic / pharmacology*
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / pharmacokinetics
  • Platelet Aggregation Inhibitors / pharmacology*
  • Platelet Function Tests
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*
  • Thiazolidines
  • Time Factors

Substances

  • Oligopeptides
  • Peptides, Cyclic
  • Platelet Aggregation Inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Thiazolidines
  • MK 0852
  • Adenosine Diphosphate
  • Collagen