Pharmacological Effects of LB30057, a New Oral Thrombin Ingibitor.

Abstract

The antithrombotic and anticoagulant effects of LB30057, an orally available, highly selective direct thrombin inhibitor, were studied to seek its therapeutic potential for the treatment of venous thrombosis. The antithrombotic effects of LB30057 after intravenous or oral application were assessed with the venors thrombosis model in rats and dogs that mimic the disorders associated with venous thrombosis. In the rat venors thrombosis model, clot at isolated segment of inferior vena cava was reduced by 50% with the applecation of 1mg /kg (5 min after i.V.), 100mg/kg (2 hr. after p.o) and 100-200mg/kg (4 hr after p.o), respectively. The weight of thrombus formed in the canine jugular vein was reduced to half by the application of 10-20mg/kg (3hr. after p.o) and 20-30mg/kg (6 hr after p.o) of LB30057. Oral application of LB30057 at 200mg/kg in rats did not couse any observable effects on aPTT and PT, while significant prologation of TT was observed upto 6.8 folds the basal at 4 hrs after treatment. Taken together, LB30057 can be a promising new therapeutic ageny of venous thrombotic disorder.