Background:

Factor Xa (FXa), a key serine protease, is a promising target enzyme for the prophylaxis and treatment of thromboembolic diseases. Edoxaban tosylate monohydrate is a novel antithrombotic agent that directly inhibits FXa activity.

In vitro: Edoxaban tosylate monohydrate (DU-176b) inhibited FXa with Ki values of 0.561 nM for free FXa, 2.98 nM for prothrombinase, and exhibited >10 000-fold selectivity for FXa. DU-176b doubled prothrombin time and activated partial thromboplastin time in human plasma. DU-176b did not impair platelet aggregation by ADP, collagen or U46619 [1].

In vivo: DU-176b dose-dependently inhibited thrombus formation in rat and rabbit thrombosis models, although bleeding time in rats was not significantly prolonged at an antithrombotic dose [1].

Clinical trial: A previous study determined the mass balance and pharmacokinetics of edoxaban in humans after oral administration of [14C]edoxaban. The mass balance of edoxaban study showed unchanged edoxaban as the most abundant component. Edoxaban was eliminated through multiple pathways, but each accounts for only a small amount of overall elimination [2].

参考文献:
[1] Furugohri T, Isobe K, Honda Y, Kamisato-Matsumoto C, Sugiyama N, Nagahara T, Morishima Y, Shibano T.  DU-176b, a potent and orally active factor Xa inhibitor: in vitro and in vivo pharmacological profiles. J Thromb Haemost. 2008;6(9):1542-9.
[2] Bathala MS, Masumoto H, Oguma T, He L, Lowrie C, Mendell J.  Pharmacokinetics, biotransformation, and mass balance of edoxaban, a selective, direct factor Xa inhibitor, in humans. Drug Metab Dispos. 2012;40(12):2250-5.