Idraparinux sodium. Anticoagulant factor Xa inhibitor

Activated factor Xa promotes coagulation by generating small amounts of thrombin in the proximity of platelets, thus enhancing their activation, and by binding to factor Va on membrane surfaces to form the prothrombinasecomplex. Due to its central role in the coagulation cascade, factor Xa is a strategic target for antithrombotic therapy and accelerating the inhibition of factor Xa is a promising approach for the treatment of thrombosis. Direct inhibitors bind directly to factor Xa inactivating both free factor Xa and factor Xa in the prothrombinase complex, while indirect inhibitors require antithrombin (AT) for their action and only inhibit the activity of free factor Xa. Pentasaccharides are synthetic indirect selective inhibitors of factor Xa that represent the smallest heparin-based molecules that retain antithrombotic activity. The first selective inhibitor of factor Xa developed from this novel group of antithrombotic compounds was fondaparinux. However, the C m a x and elimination half-life of this agent are 3 and 17-21 h, respectively. Thus. the design of new pentassacharides continues in an effort to find new compounds with improved half-lives. From a series of nonglycosaminogiycan analogs of fondaparinux sodium, idraparinux sodium was identified and shown to have potent anticoagulant activity through its ability to activate AT and accelerate the inhibition of factor Xa. idraparinux was chosen for further development for the treatment and secondary prevention of venous thromboembolic events in patiertis with deep vein thrombosis or pulmonary embolism.