Sibrafiban (RO 48-3657) is the orally active, nonpeptide, double-prodrug of Ro 44-3888 and 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 result in 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. The maximum inhibition of ex vivo platelet aggregation and prolongation of bleeding time by Ro 44-3888 are dose dependent[1].
[1]. M Dooley, et al. Sibrafiban. Drugs. 1999 Feb;57(2):225-30; discussion 231-2.
[2]. B Wittke, et al. Pharmacokinetics and pharmacodynamics of sibrafiban alone or in combination with ticlopidine and aspirin. Br J Clin Pharmacol. 2000 Mar;49(3):231-9.
[3]. Jeffrey T Billheimer, et al. Effects of glycoprotein IIb/IIIa antagonists on platelet activation: development of a transfer method to mimic peak to trough receptor occupancy. Thromb Res. 2002 Sep 15;107(6):303-17.