Betrixaban (maleate)

Betrixaban (PRT054021) maleate is a highly potent, selective, and orally efficacious factor Xa (fXa) inhibitor with an IC₅₀ of 1.5 nM. Betrixaban maleate shows antithrombotic effect^[1][3]. IC50 & Target:IC₅₀: 1.5 nM (fXa)^[1]
K_i: 0.117 nM (fXa), 1.8 μM (hERG)^[1] In Vitro:Betrixaban (PRT054021) shows IC₅₀ of 8.9 μM in patch clamp hERG assays^[1].
Betrixaban shows an IC₅₀ and a K_i of 6.3 μM and 3.5 μM for the plasma kallikrein, respectively^[1].
Betrixaban (hERG K_i 1.8 μM) exhibits significantly lower hERG activity than all the others (hERG K_i⩽0.5 μM)^[1].
Betrixaban (5-25 ng/mL) inhibits thrombin generation^[3]. In Vivo:Betrixaban (0.5 mg/kg, i.v.; 2.5 mg/kg, p.o.) has oral bioavailability of 51.6% in dog^[1].
Betrixaban (0.75 mg/kg, i.v.; 7.5 mg/kg, p.o.) has oral bioavailability of 58.7% in monkey^[1].
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%^[2].
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^[3].
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^[3].