Betrixaban is a new, long-acting, oral and selective Factor Xa inhibitor that decreases prothrombinase activity and thrombin generation.

IC50 & Target

Factor Xa (Cell-free assay)：1.5 nM

体外

In patch clamp hERG assays, Betrixaban has IC50 of 8.9 μM. The plasma kallikrein IC50 and Ki values for Betrixaban are 6.3 μM and 3.5 μM respectively. Betrixaban (hERG Ki 1.8 μM) exhibits significantly lower hERG activity than all the others (hERG Ki⩽0.5 μM).

体内

Dosed at 0.5 mg/kg IV and 2.5 mg/kg PO, Betrixaban has bioavailability of 51.6% in dog; dosed at 0.75 mg/kg IV and 7.5 mg/kg PO, Betrixaban has bioavailability of 58.7% in monkey. Both Betrixaban and Apixa-ban-mediated whole-blood INR increases are similarly reversed by r-Antidote. After i.v. infusion of the three fXa inhibitors (each admin¬istered individually) for 30 min, the total plasma concentrations of rivaroxaban, Betrixaban and apixaban are 1.4±0.4 μM (mean±s.d.), 0.2±0.01 μM and 1.4±0.3 μM, respectively, and the percentages of unbound inhibitor are 2.2%±0.8% (mean±s.d.), 40%±7.2% and 1.5%±0.3%, respectively. After administration of r-Antidote, the total plasma concentrations of the inhibitors increased to 1.9±0.09 μM, 2.0±0.4 μM and 4.2±0.7 μM, respectively, and the percentage of unbound inhibitor declined to 0%, 0.3%±0.1% and 0.05%±0.02%, respectively. Thus, for each of the three inhibitors, correction of prothrombin time by r-Antidote to near-normal values is associated with a reduction in the free fraction of the inhibitor.

Rivaroxaban (BAY 59-7939)

MB1879

Apixaban (BMS 562247-01)

MB5017

Edoxaban

1 mg

5 mg

10 mg

1 mM

2.2128 mL

11.0641 mL

22.1283 mL

5 mM

0.4426 mL

2.2128 mL

4.4257 mL

10 mM

0.2213 mL

1.1064 mL

2.2128 mL

50 mM

0.0443 mL

0.2213 mL

0.4426 mL