Favorable therapeutic index of the direct factor Xa inhibitors, apixaban and rivaroxaban, compared with the thrombin inhibitor dabigatran in rabbits.

摘要: Summary. Background: Apixaban is an oral, direct factor Xa (FXa) inhibitor in late-stage clinical development. This study assessed effects of the FXa inhibitors, apixaban and rivaroxaban, vs. thrombin inhibitor, dabigatran, on venous thrombosis (VT), bleeding time (BT) clotting times rabbits. Methods: We induced formation non-occlusive thrombus VT models by placing threads vena cava, incision cuticles anesthetized Apixaban, rivaroxaban dabigatran were infused IV to achieve a stable plasma level. Clotting times, including activated partial thromboplastin (aPTT), prothrombin (PT), modified PT (mPT) (TT), measured. Results: exhibited dose-related efficacy preventing with EC50 65, 33 194 nm, respectively. At doses for 80% reduction control thrombus, apixaban, prolonged BT 1.13 ± 0.02-, 1.9 ± 0.1-* 4.4 ± 0.4-fold*, respectively (*P < 0.05, apixaban). In treatment model, these inhibitors equally prevented growth preformed thrombus. Antithrombotic aPTT <3-fold no effect TT. Dabigatran was ≥50-fold more potent prolonging TT than PT. Of assays studied, responded best mPT. Conclusion: Comparable antithrombotic observed between prevention lower compared at equivalent doses. The significance findings remains be determined.