title: Successful attenuation of venous thrombus growth in rabbits after the administration of a novel oral thrombin inhibitor.
abstract: Current antithrombotic compounds have several limitations in clinical practice. The present study was designed to investigate a novel orally available direct thrombin inhibitor, BSF 208791. Intravenous administration of BSF 208791 showed superior antithrombotic properties as compared with Polyethylenglycol-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, respectively. Moreover, bleeding time was less affected after administration of BSF 208791 as compared with PEG-Hirudin. The oral administration of BSF 208791 resulted in adequate bioavailability and significantly reduced venous 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-Hiridin and LMWH without affecting the bleeding time. BSF 208791 is an orally available agent that might be a promising candidate for future antithrombotic therapy.
authors: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, The Netherlands. p.w.friederich@amc.uva.nl
authors: P W
authors: PW
authors: Friederich
authors: T T
authors: TT
authors: Keller
authors: B J
authors: BJ
authors: Biemond
authors: R J
authors: RJ
authors: Peters
authors: W
authors: W
authors: Hornberger
authors: H R
authors: HR
authors: Büller
authors: M
authors: M
authors: Levi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage; D000991:Antithrombins / Q000008:administration & dosage*; D004195:Disease Models, Animal; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage; D006629:Hirudins / Q000008:administration & dosage / Q000031:analogs & derivatives; D009842:Oligopeptides / Q000008:administration & dosage; D011817:Rabbits; D013927:Thrombosis / Q000188:drug therapy*
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; C424243:BSF 208791; D006495:Heparin, Low-Molecular-Weight; D006629:Hirudins; D009842:Oligopeptides; C104614:polyethyleneglycol-hirudin