In vivo efficacy of SM-20302, a GP IIb/IIIa receptor antagonist, correlates with ex vivo platelet inhibition in heparinized blood but not in citrated blood

Arteriosclerosis, Thrombosis, and Vascular Biology
S S RebelloB R Lucchesi

Abstract

We tested the hypothesis that the in vivo antithrombotic efficacy of SM-20302, a GP IIb/IIIa receptor antagonist, correlates with the ex vivo platelet inhibition in heparinized platelet rich plasma (hPRP) but not in citrated PRP (cPRP). The studies were performed in a canine model of carotid artery thrombosis in which thrombus formation was induced by electrolytic injury. Thrombosis of the right carotid artery was induced immediately after the administration of saline (n=12). Thirty minutes after persistent occlusive thrombosis was obtained, the vessel segment was ligated, and the time to occlusion and thrombus weight were noted. Subsequently, thrombosis of the left carotid artery was initiated in the presence of SM-20302 (100, 300, 600, or 1000 microg/kg i.v.; n=4 to 6). All the doses of SM-20302 inhibited (by > or = 90%) the ex vivo platelet aggregation induced by ADP and arachidonic acid (AA) in cPRP. In hPRP, a dose-dependent inhibition of ex vivo platelet aggregation was observed. The maximal inhibition produced by 100 to 1000 microg/kg SM-20302 ranged from 18% to 80% for ADP and 44% to 88% for AA. Maximal prolongation of the template bleeding time induced by the 100-, 300-, 600-, and 1000-microg/kg doses were 2.5-, 9.5-, ...Continue Reading

References

Jan 1, 1990·Annual Review of Cell Biology·N Kieffer, D R Phillips
Feb 6, 1990·Biochemistry·R HeidenreichM Poncz
Nov 15, 1988·Thrombosis Research·J L Pérez RequejoJ Aznar
Aug 1, 1995·Journal of Cardiovascular Pharmacology·Y SudoB R Lucchesi
Jun 8, 1995·The New England Journal of Medicine·J LefkovitsE J Topol
Jan 15, 1996·Thrombosis Research·P DandonaS Mousa

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Citations

Sep 11, 1998·Journal of Cardiovascular Pharmacology·S S RebelloB R Lucchesi
Jun 27, 2003·Journal of Cardiovascular Pharmacology·James K HennanBenedict R Lucchesi
Sep 29, 1999·American Heart Journal·N S Kleiman

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