5-R-Rivaroxaban is a selective inhibitor of human Factor Xa with IC50 value of 0.7 nmol/L [1].
Factor Xa is a serine endopeptidase enzyme and plays an important role in the convergence point of the intrinsic and extrinsic pathways in blood coagulation system [2].
5-R-Rivaroxaban is an oral, direct factor Xa inhibitor and the inhibition is species-dependent. When tested with purified factoe Xa from human or rabbit, 5-R-Rivaroxaban showed similar affinity with IC50 value of 0.7 nmol/L and 0.8 nmol/L, respectively, while had a IC50 value as low as 3.4 nmol/L when tested with rat factor Xa [1].
Pre-treated anaesthetised rat model with intravenous 5-R-Rivaroxaban at a dose of 2 mg/kg, and after bleeding initiated intravenous treated with rFVIIa (100/400 μg/kg), PCC (25/50 U/kg) or aPCC (50/100 U/kg), the result showed that 5-R-Rivaroxaban pre-treatment significantly shorten bleeding time and clotting time compared with 5-R-Rivaroxaban alone treated group [2]. Similar results were obtained when tested with rabbit model [1].
It has been reported that 5-R-Rivaroxaban is a promising drug for atrial fibrillation, venous thromboembolism or thromboembolic disorders in clinic [3] [4] [1].
References:
[1]. Perzborn, E., et al., Rivaroxaban: a new oral factor Xa inhibitor. Arterioscler Thromb Vasc Biol, 2010. 30(3): p. 376-81.
[2]. Perzborn, E., et al., Reversal of rivaroxaban anticoagulation by haemostatic agents in rats and primates. Thromb Haemost, 2013. 110(1): p. 162-72.
[3]. Beyer-Westendorf, J., et al., Efficacy and safety of rivaroxaban or fondaparinux thromboprophylaxis in major orthopedic surgery: findings from the ORTHO-TEP registry. J Thromb Haemost, 2012. 10(10): p. 2045-52.
[4]. Palareti, G., et al., Clinical management of rivaroxaban-treated patients. Expert Opin Pharmacother, 2013. 14(5): p. 655-67.
