Sibrafiban (RO 48-3657) is the orally active, nonpeptide, double-prodrug of Ro 44-3888 which is a selective glycoprotein IIb/IIIa receptor antagonist. Sibrafiban inhibits platelet aggregation [1] [2] [3].

The effects of site occupancy by Sibrafiban on platelet activation are assessed using P-selectin expression, fibrinogen binding and microaggregate formation. Sibrafiban inhibits ADP and TRAP-stimulated fibrinogen binding and microaggregate formation in a concentration-dependent manner, whereas P-selectin expression is relatively unaltered. A decrease in site occupancy from peak to trough of Sibrafiban does not cause increased activation of platelets [3].

The effects of Ro 44-3888 on the platelet aggregation response to ADP (17 μmol) and on cutaneous bleeding times is determined in 8 rhesus monkeys given Sibrafiban 0.25 mg/kg/day or 0.5 mg/kg/day orally for 8 days. Ro 44-3888 showed a dose-dependent maximum inhibition of ex vivo platelet aggregation and prolongation of bleeding time [1].