Direct Factor Xa Inhibitors in Clinical Development

Factor Xa inhibitors currently being evaluated in clinical trials are listed in Table 4. Among the most advanced in clinical development are rivaroxaban (Johnson & Johnson Pharmaceutical Research & Development, Raritan, NJ) and apixaban (Bristol-Myers Squibb, New York, NY).

Rivaroxaban is a selective competitive direct factor Xa inhibitor with high bioavailability (60-80%) (Kubitza and Haas, 2006). Maximum plasma drug levels occur 2-3 h after oral administration, and the terminal half-life is 6-9 h. It is excreted by both renal (66%) and fecal/biliary (28%) routes, and is administered once or twice daily. Rivaroxaban causes dose-dependent prolongation of the PT and aPTT (Kubitza and Haas, 2006). Rivaroxaban has shown promising results in phase II trials for the prevention and treatment of VTE in patients undergoing orthopedic surgery and is currently being tested in phase II trials for the management of ACS, in phase III trials for the prevention and treatment of VTE, and in phase III trials for the prevention of stroke or systemic embolism in patients with atrial fibrillation (AF).

Razaxaban is an orally active direct factor Xa inhibitor that was being developed by Bristol-Myers Squibb, but was discontinued after the three higher doses in a dose ranging study to prevent VTE were stopped because of increased bleeding (Kubitza and Haas, 2006). Apixaban is a follow-up compound to raza-xaban and is currently entering clinical trials for the prevention of VTE, for the management of ACS, and for the prevention of stroke or systemic embolism in patients with AF.

0 0

Post a comment