title: Protective effects of DX-9065a, an orally active, novel synthesized and selective inhibitor of factor Xa, against thromboplastin-induced experimental disseminated intravascular coagulation in rats.
abstract: We investigated the protective effects of DX-9065a, an orally active, newly synthesized, and specific inhibitor of factor Xa, against experimental disseminated intravascular coagulation (DIC) in rats. Experimental DIC was induced by a 4 hour sustained infusion of thromboplastin at a dose of 2.5 mg/kg. The rats were orally administered DX-9065a at 10, 30, 100 mg/kg 30 minutes before thromboplastin injection. In this DIC model, DX-9065a showed a protective effect against DIC, at all doses and in all parameters, including fibrin(ogen) degradation products, fibrinogen level, thrombin-antithrombin III complex level, prothrombin time (PT), activated partial thromboplastin time (APTT), platelet count, and the number of renal glomeruli with fibrin thrombi. When DX-9065a was orally administered at 100 mg/kg without thromboplastin, no significant changes were seen in hemostatic parameters except PT and APTT, and no fibrin thrombi or abnormal bleeding were seen in renal specimens. These findings suggested that the new oral anti-Xa drug, DX-9065a, has a protective effect against thromboplastin-induced DIC model with little risk of bleeding.
authors.affiliation: Department of Internal Medicine (III), Kanazawa University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yamazaki
authors.forename: H
authors.initials: H
authors.lastname: Asakura
authors.forename: K
authors.initials: K
authors.lastname: Aoshima
authors.forename: M
authors.initials: M
authors.lastname: Saito
authors.forename: H
authors.initials: H
authors.lastname: Jokaji
authors.forename: C
authors.initials: C
authors.lastname: Uotani
authors.forename: I
authors.initials: I
authors.lastname: Kumabashiri
authors.forename: E
authors.initials: E
authors.lastname: Morishita
authors.forename: T
authors.initials: T
authors.lastname: Ikeda
authors.forename: T
authors.initials: T
authors.lastname: Matsuda
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation / Q000139:chemically induced / Q000188:drug therapy*; D005170:Factor X / Q000037:antagonists & inhibitors*; D065427:Factor Xa Inhibitors; D008297:Male; D009281:Naphthalenes / Q000008:administration & dosage*; D011422:Propionates / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D013925:Thromboplastin / Q000008:administration & dosage
chemical_list: C086910:(2S)-2-(4-(((3S)-1-acetimidoyl-3-pyrrolidinyl)oxy)phenyl)-3-(7-amidino-2-naphtyl)propanoic acid; D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D009281:Naphthalenes; D011422:Propionates; D005170:Factor X; D013925:Thromboplastin