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

Howard E. Greenberg, Paul Wissel, Jeffrey Barrett, Aaron Barchowsky, Robert Gould, Daniel Farrell, Deborah Panebianco, Elizabeth Hand, Lisa Gillen, Michael R. Goldberg, Thorir D. Bjornsson

Research output: Contribution to journalArticle

5 Scopus citations

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 μg/kg/min for 1 hour and 0.44 μg/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. (C) 2000 the American College of Clinical Pharmacology.

Original languageEnglish (US)
Pages (from-to)496-507
Number of pages12
JournalJournal of Clinical Pharmacology
Volume40
Issue number5
DOIs
StatePublished - Jan 1 2000

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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    Greenberg, H. E., Wissel, P., Barrett, J., Barchowsky, A., Gould, R., Farrell, D., Panebianco, D., Hand, E., Gillen, L., Goldberg, M. R., & Bjornsson, T. D. (2000). Antiplatelet effects of MK-852, a platellet fibrinogen receptor antagonist, in healthy volunteers. Journal of Clinical Pharmacology, 40(5), 496-507. https://doi.org/10.1177/00912700022009116