DX-9065a, an orally active, specific inhibitor of factor Xa, inhibits thrombosis without affecting bleeding time in rats.
We evaluated the antithrombotic effects of DX-9065a, a specific factor Xa inhibitor, using tissue thromboplastin-induced DIC (TP-DIC) and the arterio-venous shunt (AV shunt) in rats. Intravenous TP injection reduced the platelet counts and fibrinogen concentrations in blood. In the TP-DIC model, an intravenous dose of DX-9065a 0.23 mg/kg 1 min before TP injection suppressed the consumption of platelets and fibrinogen to 57% and 66%, respectively, and the production of FDP almost completely. In the AV shunt model, DX-9065a inhibited thrombus formation to 51% on intravenous administration of 0.23 mg/kg and to 60% when given orally at 23.3 mg/kg. Intravenous administration of 2.33 mg/kg of DX-9065a did not affect the bleeding time. These results suggest that Xa inhibition may be an appropriate approach for suppressing thrombosis without impairing haemostasis.
Hara
T
T
Exploratory Research Laboratories II, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Yokoyama
A
A
Tanabe
K
K
Ishihara
H
H
Iwamoto
M
M
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology* / Q000627:therapeutic use; D001166:Arteriovenous Shunt, Surgical; D001760:Bleeding Time; D001777:Blood Coagulation / Q000187:drug effects*; D004211:Disseminated Intravascular Coagulation / Q000139:chemically induced / Q000188:drug therapy; D065427:Factor Xa Inhibitors; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005340:Fibrinogen / Q000032:analysis; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology* / Q000627:therapeutic use; D010976:Platelet Count / Q000187:drug effects; D011422:Propionates / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013925:Thromboplastin / Q000633:toxicity
C086910:(2S)-2-(4-(((3S)-1-acetimidoyl-3-pyrrolidinyl)oxy)phenyl)-3-(7-amidino-2-naphtyl)propanoic acid; D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D005338:Fibrin Fibrinogen Degradation Products; D009281:Naphthalenes; D011422:Propionates; D005340:Fibrinogen; D013925:Thromboplastin