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Thromb Haemost 2000; 84(05): 858-864
DOI: 10.1055/s-0037-1614128
Review Article
Schattauer GmbH

Successful Attenuation of Venous Thrombus Growth in Rabbits after the Administration of a Novel Oral Thrombin Inhibitor

Philip W. Friederich
1   From the Departments of Vascular Medicine, University of Amsterdam, Amsterdam, The Netherlands
2   Internal Medicine, University of Amsterdam, Amsterdam, The Netherlands
,
Tymen T. Keller
1   From the Departments of Vascular Medicine, University of Amsterdam, Amsterdam, The Netherlands
,
Bart J. Biemond
1   From the Departments of Vascular Medicine, University of Amsterdam, Amsterdam, The Netherlands
2   Internal Medicine, University of Amsterdam, Amsterdam, The Netherlands
,
Ron J. G. Peters
3   Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
,
Wilfried Hornberger
4   Department of Experimental and Cardiovascular Research, Knoll AG, Ludwigshafen, Germany
,
Harry R. Büller
1   From the Departments of Vascular Medicine, University of Amsterdam, Amsterdam, The Netherlands
,
Marcel Levi
1   From the Departments of Vascular Medicine, University of Amsterdam, Amsterdam, The Netherlands
2   Internal Medicine, University of Amsterdam, Amsterdam, The Netherlands
› Author AffiliationsMarcel Levi is a fellow of the Royal Netherlands Academy of Arts and Sciences; Harry Büller is an established investigator of the Netherlands Heart Foundation and Philip Friederich is supported by a grant from the Netherlands Organization for Scientific Research (NWO).
Further Information

Publication History

Received 07 February 2000

Accepted after resubmission 24 May 2000

Publication Date:
13 December 2017 (online)

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Summary

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-Hirudin and LMWH without affecting the bleeding time. BSF 208791 is an orally available agent that might be a promising candidate for future antithrombotic therapy.

Key words

Anticoagulants - thrombosis - coagulation - rabbits - thrombin inhibitor
 

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