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[摘要]：Deep vein thrombosis and related complications ore important contributors to mortality and morbidity and represent a major public health concern. New orally active small molecules with powerful and reliable antithrombotic actions ore being developed as currently available onticoagulant strategies have limitations. Factor Xa has emerged as a particularly promising target for effective anticoagulation because it acts at the convergence point of the intrinsic and extrinsic coagulation pathways. Edoxaban tosilate (DU-776b), on oral, direct and highly specific inhibitor of activated factor Xa, has no effect on the enzymatic activities of other serine proteases. The antithrombotic action of edoxaban has been demonstrated both in vitro and in vivo, in experimental models of arterial and venous thrombosis in different animal species, A 10-fold dissociation between antithrombotic and bleeding effects was predicted from different animal models. Edoxaban has a favoroble pharmacokinetic profile in humans, reaching a maximal concentration 1-2 h after oral administration with an elimination half-life of 9-11 h, and is predominantly renally secreted. Data from early clinical studies indicate that edoxaban is safe and effective in preventing thrombotic events in patients after elective total knee arthroplasty and unilateral hip replacement. Phase II studies hove investigated safety, efficacy and dose response relationships in patients with nonvalvular atrial fibrillation with encouraging results. Phase III studies ore currently underway to confirm the safety and effectiveness of edoxaban versus the standard treatment warfarin in patients with atrial fibrillation. |
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