Successful attenuation of venous thrombus growth in rabbits after the administration of a novel oral thrombin inhibitor

Current antithrombotic compounds have several limitations in clinical pract ice. The present study was designed to investigate a novel orally available direct thrombin inhibitor, BSF 208791. Intravenous administration of BSF 2 08791 showed superior antithrombotic properties as compared with Polyethyle nglycol-Hirudin (PEG-Hirudin) and low molecular weight heparin (LMWH) in a model of venous thrombosis in rabbits. The thrombus growth was 22%, 30%, 37 % and 50% after BSF 208791,PEG-Hirudin, LMWH, and saline administration, re spectively. Moreover, bleeding time was less affected after administration of BSF 208791 as compared with PEG-Hirudin. The oral administration of BSE 208791 resulted in adequate bioavailability and significantly reduced venou s thrombus growth to 36% as compared with 60% in the saline treated rabbits . The antithrombotic effect of BSF 208791 appears to be superior to PEG-Hir udin and LMWH without affecting the bleeding time. BSF 208791 is an orally available agent that might be a promising candidate for future antithrombot ic therapy.