330942-05-7

In patch clamp hERG assays, Betrixaban has IC ₅₀ of 8.9 μM. The plasma kallikrein IC ₅₀ and K _i values for Betrixaban are 6.3 μM and 3.5 μM respectively. Betrixaban (hERG K _i 1.8 μM) exhibits significantly lower hERG activity than all the others (hERG K _i ⩽0.5 μM).

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.