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  • Title: Pharmacokinetics and pharmacodynamics of sibrafiban, an orally administered GP IIb/IIIa antagonist, following coadministration of aspirin and heparin.
    Author: Reimann JD, Modi NB, Novotny W.
    Journal: J Clin Pharmacol; 2000 May; 40(5):488-95. PubMed ID: 10806602.
    Abstract:
    Sibrafiban is a double prodrug that is converted to the inactive single prodrug and to the active GP IIb/IIIa antagonist after oral administration. This clinical investigation evaluated whether coadministration of oral aspirin or intravenous heparin would alter the pharmacokinetics or pharmacodynamics of oral sibrafiban. Twenty-four adult subjects received two of the following four combinations: sibrafiban alone, sibrafiban with ASA, sibrafiban with heparin, and sibrafiban with ASA and heparin, separated by a 2-week washout period. Concentration profiles of active drug in citrate and EDTA plasma were unchanged with coadministration of ASA or heparin. No pharmacodynamic interaction was seen with coadministration of heparin. Inhibition of platelet aggregation increased 4% to 55%, and Ivy bleeding time increased 58% to 87% with coadministration of sibrafiban and ASA. The combined pharmacodynamic effect of sibrafiban and ASA may indicate a potentially greater therapeutic effect but an increased risk of bleeding when these drugs are used in combination.
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