DX-9065a, an orally active, specific inhibitor of factor Xa, inhibits thrombosis without affecting bleeding time in rats

Thromb Haemost. 1995 Aug;74(2):635-9.

Abstract

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.

MeSH terms

  • Animals
  • Anticoagulants / pharmacology*
  • Anticoagulants / therapeutic use
  • Arteriovenous Shunt, Surgical
  • Bleeding Time
  • Blood Coagulation / drug effects*
  • Disseminated Intravascular Coagulation / chemically induced
  • Disseminated Intravascular Coagulation / drug therapy
  • Factor Xa Inhibitors*
  • Fibrin Fibrinogen Degradation Products / analysis
  • Fibrinogen / analysis
  • Male
  • Naphthalenes / pharmacology*
  • Naphthalenes / therapeutic use
  • Platelet Count / drug effects
  • Propionates / pharmacology*
  • Propionates / therapeutic use
  • Rats
  • Rats, Wistar
  • Thromboplastin / toxicity

Substances

  • (2S)-2-(4-(((3S)-1-acetimidoyl-3-pyrrolidinyl)oxy)phenyl)-3-(7-amidino-2-naphtyl)propanoic acid
  • Anticoagulants
  • Factor Xa Inhibitors
  • Fibrin Fibrinogen Degradation Products
  • Naphthalenes
  • Propionates
  • Fibrinogen
  • Thromboplastin