Cell lines

Human, rabbit and rat plasma

Preparation method

The solubility of this compound in DMSO is >20.85mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

IC50: 21 nM (human and rabbit plasma)

Applications

Rivaroxaban competitively inhibited human FXa with the Ki value of 0.4 nM. Rivaroxaban inhibited prothrombinase activity with the IC50 of 2.1 nM. Rivaroxaban inhibited endogenous FXa more potently in human and rabbit plasma (IC50: 21 nM) than rat plasma (IC50:290 nM). Rivaroxaban demonstrated anticoagulant effects in human plasma, doubling prothrombin time (PT) and activated partial thromboplastin time at 0.23 and 0.69 μM, respectively.

Animal models

Rat venous stasis model, Anaesthetised rat model

Dosage form

Intravenous inection, Oral administration, 2 mg/kg

Application

In a rat venous stasis model, Rivaroxaban (i.v.) dose-dependently reduced venous thrombosis with the ED50 of 0.1 mg/kg. Rivaroxaban (p.o.) reduced arterial (fibrin- and platelet-rich) thrombus formation in an arteriovenous (AV) shunt in rats (ED50: 5 mg/kg) and rabbits (ED50: 0.6 mg/kg). In anaesthetised rat model, pretreatment with 5-R-Rivaroxaban (i.v., 2 mg/kg) shortened bleeding time and clotting time.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

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.