Betrixaban

Biological Activity

Betrixaban is a highly potent, selective, and orally efficacious factor Xa inhibitor with IC50 of 1.2 nM(inhibition of Factor 10a).Betrixaban is an oral direct inhibitor being developed for the prevention of venous thromboembolism (VTE).Betrixaban demonstrates antithrombotic activity and appeared well tolerated in knee replacement patients at the doses studied.

Customer Product Validations & Biological Datas

	Source	Expert Opin Pharmacother (2013). Figure 2. Betrixaban
	Method	PK--PD analysis
	Cell Lines
	Concentrations	27.7 ng/mL and 58.6 ng/mL
	Incubation Time	3.17 h
	Results	The median time of maximum plasma concentration (Tmax) for betrixaban occurred at 3.17 h after dosing for both dose groups

	Source	Expert Opin Pharmacother (2013). Figure 1. Betrixaban
	Method	PK--PD analysis
	Cell Lines
	Concentrations	27.7 ng/mL and 58.6 ng/mL
	Incubation Time	3.17 h
	Results	The PK--PD modeling results demonstrated that betrixaban had no effect on cardiac repolarization

Protocol

Cell Experiment
Cell lines	whole blood
Preparation method	In a tissue factor-induced thrombin generation assay, betrixaban in concentrations ranging from 5 ng/mL to 25 ng/mL inhibited thrombin generation to a comparable degree as trough, and the peak levels were achieved by 2.5 mg fondaparinux.
Concentrations	5 ng/mL to 25 ng/mL
Incubation time	3–4 h

Animal Experiment
Animal models	rabbit vena cava
Formulation	0.5% methylcellulose
Dosages	3 mg/kg
Administration	i.v.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information

References

Profile of betrixaban and its potential in the prevention and treatment of venous thromboembolism
Chan NC, et al. Vasc Health Risk Manag. 2015 Jun 26;11:343-51. PMID: 26170684.

A randomized evaluation of betrixaban, an oral factor Xa inhibitor, for prevention of thromboembolic events after total knee replacement (EXPERT).
Turpie AG,et al. Thromb Haemost. 2009 Jan;101(1):68-76. PMID: 19132191.