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

The impact of Sibrafiban on platelet activation is evaluated through measures of P-selectin expression, fibrinogen binding, and microaggregate formation. Sibrafiban concentration-dependently inhibits both ADP and TRAP-induced fibrinogen binding and microaggregate formation, while having minimal effect on P-selectin expression. Furthermore, a reduction in Sibrafiban's site occupancy does not lead to an increase in platelet activation [3].

The activity of Ro 44-3888 on both ADP-induced platelet aggregation (17 μmol) and cutaneous bleeding duration was assessed in eight rhesus monkeys administered Sibrafiban at dosages of 0.25 mg/kg/day or 0.5 mg/kg/day through oral administration over eight days. Results demonstrated that Ro 44-3888 exhibits a dose-dependent maximal inhibition of ex vivo platelet aggregation alongside an extension of bleeding time [1].