PHARMACODYNAMIC INTERACTION: GPIIB/IIIA ANTAGONIST/ASPIR

$0M01FY2000RRNIH

University Of Pennsylvania, Philadelphia PA

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Abstract

The purpose of this study is to investigate the pharmacodynamic interaction between the platelet glycoprotein IIb/IIIa antagonists (i.e. RPR 109891) and aspirin. The in vitro effects of the GPIIb/IIIa antagonist alone and the GPIIb/IIIa antagonist in aspirinated blood will be assessed by platelet GPIIb/III receptor occupancy, platelet agglutination, platelet-dependent hemostasis and inhibition of platelet aggregation. We have assessed the comparative effects of RPR 109039, the active metabolite of KLERVCAL, (+/- aspirin) in vitro and PA and two novel indices of receptor antagonism: receptor occupancy (RO) by the Biocytex double antibody assay and platelet-dependent homostatis by the Date Platelet Function Analyzer (PFA-100). Following aspirin intake, the additive effect on PA and RO was more pronounced at low doses (23+/-5% inhibition of ADP-induced aggregation and 21+/-7% of occupied receptors at 10 ng/ml). An additive inhibition of platelet function was also observed by PFA-100 (252+/-43% increase over baseline in RPR 109039, 50 ng/ml). Extrapolation of this technology to large scale multi-center studies of chronic GP IIb/IIIa antagonists will permit investigation of drug interaction and correlation of quantitative indices of receptor blockade with clinical outcome.

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