title: Treatment of venous thrombosis with an oral direct factor Xa inhibitor edoxaban by single and multiple administrations in rats.
abstract: 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 5min. 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 4h 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 10mg/kg) 1h after thrombus formation significantly regressed the venous thrombus compared to the thrombus at 1h after thrombus formation. Similarly the significant venous thrombus regression was observed with enoxaparin (10mg/kg) and fondaparinux (0.30-3.0mg/kg). In the multiple administration experiment, both QD and BID administration of edoxaban at daily doses of 5 and 10mg/kg exerted significant treatment effects. QD administration of edoxaban including lower doses (1-10mg/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.
authors.affiliation: Biological Research Laboratories, R & D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. Electronic address: morishima.yoshiyuki.t4@daiichisankyo.co.jp.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Morishima
authors.affiliation: Biological Research Laboratories, R & D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Kamisato
authors.affiliation: Biological Research Laboratories, R & D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Honda
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage; D000990:Antithrombin III; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D017984:Enoxaparin / Q000008:administration & dosage; D065427:Factor Xa Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000077425:Fondaparinux; D008297:Male; D010447:Peptide Hydrolases / Q000097:blood; D011134:Polysaccharides / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D020246:Venous Thrombosis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D011134:Polysaccharides; D011725:Pyridines; D013844:Thiazoles; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D010447:Peptide Hydrolases; D000077425:Fondaparinux; C552171:edoxaban
keywords: Animal models; Edoxaban tosilate hydrate (PubChem CID: 25022378); Edoxaban.; Enoxaparin (PubChem CID: 772); Factor Xa inhibitor; Fondaparinux (PubChem CID: 636380); Oral anticoagulant; Treatment effect; Venous thrombosis