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

Philip W. Friederich; Tymen T. Keller; Bart J. Biemond; Ron J. G. Peters; Wilfried Hornberger; Harry R. Büller; Marcel Levi

doi:10.1055/s-0037-1614128

Thrombosis and Haemostasis, Table of Contents

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

¹From the Departments of Vascular Medicine, University of Amsterdam, Amsterdam, The Netherlands

²Internal Medicine, University of Amsterdam, Amsterdam, The Netherlands

,

Tymen T. Keller

¹From the Departments of Vascular Medicine, University of Amsterdam, Amsterdam, The Netherlands

,

Bart J. Biemond

¹From the Departments of Vascular Medicine, University of Amsterdam, Amsterdam, The Netherlands

²Internal Medicine, University of Amsterdam, Amsterdam, The Netherlands

,

Ron J. G. Peters

³Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

,

Wilfried Hornberger

⁴Department of Experimental and Cardiovascular Research, Knoll AG, Ludwigshafen, Germany

,

Harry R. Büller

¹From the Departments of Vascular Medicine, University of Amsterdam, Amsterdam, The Netherlands

,

Marcel Levi

¹From the Departments of Vascular Medicine, University of Amsterdam, Amsterdam, The Netherlands

²Internal Medicine, University of Amsterdam, Amsterdam, The Netherlands

› Author Affiliations

Abstract

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

Full Text

References

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