Treatment of venous thrombosis with an oral direct factor Xa inhibitor edoxaban by single and multiple administrations in rats

Edoxaban is an oral and direct activated factor X inhibitor. In this study, the acute treatment effect of edoxaban on venous thrombosis is investigated in rats by single and multiple administrations, and compared to the conventional parenteral anticoagulants, enoxaparin and fondaparinux. Venous thrombus was induced in the inferior vena cava by partial stenosis plus topical application of 10% ferric chloride for 5 min. After 1-h thrombus maturation, oral edoxaban and subcutaneous enoxaparin and fondaparinux were given. In the single administration experiment, thrombus weight was measured 1 or 4 h after thrombus induction. In the multiple administration experiments, edoxaban was orally administered once daily (QD) and twice daily (BID) for 3 days. In the single administration experiment, oral administration of edoxaban (3.0 and 10 mg/kg) 1 h after thrombus formation significantly regressed the venous thrombus compared to the thrombus at 1 h after thrombus formation. Similarly the significant venous thrombus regression was observed with enoxaparin (10 mg/kg) and fondaparinux (0.30-3.0 mg/kg). In the multiple administration experiment, both QD and BID administration of edoxaban at daily doses of 5 and 10 mg/kg exerted significant treatment effects. QD administration of edoxaban including lower doses (1-10 mg/kg) significantly reduced thrombus weight. Edoxaban administered QD and BID was effective in the treatment of venous thrombosis, and the treatment effect of edoxaban was comparable to the conventional parenteral anticoagulants. These data demonstrate the potential of edoxaban as an oral anticoagulant in the acute treatment of venous thromboembolism.