title: Betrixaban (PRT054021): pharmacology, dose selection and clinical studies.
abstract: The recently introduced oral anticoagulants, dabigatran, rivaroxaban and apixaban, were shown, in randomized controlled trials, to be at least as effective and safe as monitored warfarin therapy for the treatment of venous thromboembolism and stroke prevention in atrial fibrillation. These new oral anticoagulants have predictable pharmacology, less variability in anticoagulant effect and fewer drug and food interactions than warfarin, allowing unmonitored and fixed dosing, which renders their use appealing. The remaining limitations of currently available new oral anticoagulants include their dependence on renal and hepatic clearance, and the lack of an antidote, which is problematic in bleeding patients and those requiring urgent surgery. Betrixaban is a new direct factor Xa inhibitor with distinct pharmacological characteristics, including a long half-life, minimal renal clearance and minimal hepatic metabolism. Betrixaban was tested in Phase II studies in orthopedic thromboprophylaxis (EXPERT) and atrial fibrillation (EXPLORE-Xa), and is being evaluated in a Phase III trial of extended thromboprophylaxis in medical patients (APEX). This article details the pharmacology, preclinical and clinical development of betrixaban.
authors.affiliation: Thrombosis & Atherosclerosis Research Institute, C3-10 DBCVRSI, Hamilton General Hospital, 237 Barton Street East, Hamilton, ON L8L 2X2, Canada.
authors.forename: Noel C
authors.initials: NC
authors.lastname: Chan
authors.forename: Jack
authors.initials: J
authors.lastname: Hirsh
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Ginsberg
authors.forename: John W
authors.initials: JW
authors.lastname: Eikelboom
mesh_terms: D001281:Atrial Fibrillation / Q000150:complications*; D001549:Benzamides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*; D054556:Venous Thromboembolism / Q000209:etiology / Q000517:prevention & control*
chemical_list: D001549:Benzamides; D011725:Pyridines; C543086:betrixaban