Betrixaban maleate

Betrixaban is a non-vitamin K oral anticoagulant whose action is driven by the competitive and reversible inhibition of the factor Xa. It was selected among all lead compounds due to its low hERG channel affinity while sustaining its factor Xa inhibition capacity. Betrixaban now developed by Portola Pharmaceuticals Inc. is prescribed as a venous thromboembolism (VTE) prophylactic for adult patients with moderate to severe restricted motility or with other risks for VTE. VTE can be manifested as deep vein thrombosis or pulmonary embolism and it is a leading cause of preventable death in hospitalized patients.(In Vitro):Betrixaban (PRT054021) shows IC50 of 8.9 μM in patch clamp hERG assays.Betrixaban shows an IC50 and a Ki of 6.3 μM and 3.5 μM for the plasma kallikrein, respectively.Betrixaban (hERG Ki 1.8 μM) exhibits significantly lower hERG activity than all the others (hERG Ki 0.5 μM).Betrixaban (5-25 ng/mL) inhibits thrombin generation.(In Vivo):Betrixaban (0.5 mg/kg, i.v.; 2.5 mg/kg, p.o.) has oral bioavailability of 51.6% in dog.Betrixaban (0.75 mg/kg, i.v.; 7.5 mg/kg, p.o.) has oral bioavailability of 58.7% in monkey.Betrixaban mediated whole-blood INR increase is reversed by r-Antidote. After i.v. infusion for 30 min, the total plasma concentrations of Betrixaban is 0.2±0.01 μM, and the percentages of unbound inhibitor is 40%±7.2%. After administration of r-Antidote, the total plasma concentration increased to 2.0±0.4 μM, and the percentage of unbound inhibitor declined to 0.3%±0.1%.Betrixaban (3 mg/kg) shows nearly comparable inhibition of thrombus mass to enoxaparin 1.6 mg/kg (76% vs 96% inhibition) in the rabbit abdominal vena cava model of clot accretion on cotton threads.Betrixaban (19.1 mg/kg) is at least as effective at maintaining patency as enoxaparin 7.6 mg/kg and clopidogrel 3 mg/kg/d (90% vs 70% vs 80% patency, respectively) in the ferric chloride injury model of rodent carotid artery.