Antithrombotic Efficacy in a Rat Model of the Low Molecular Weight Heparin, Reviparin Sodium, Administered by the Oral Route

Linda M. Hiebert; Sandra M. Wice; Tilly Ping; Dieter Herr; Volker Laux

doi:10.1055/s-0037-1612913

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2001; 85(01): 114-118
DOI: 10.1055/s-0037-1612913

Review Article

Schattauer GmbH

Antithrombotic Efficacy in a Rat Model of the Low Molecular Weight Heparin, Reviparin Sodium, Administered by the Oral Route

Authors

Linda M. Hiebert

¹Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, Canada
Sandra M. Wice

¹Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, Canada
Tilly Ping

¹Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, Canada
Dieter Herr

²Knoll AG, Ludwigshafen, Germany
Volker Laux

²Knoll AG, Ludwigshafen, Germany

Abstract

Summary

Previous studies in rats show that unfractionated heparin and the low molecular weight heparin logiparin have a dose-dependent antithrombotic effect and are found in endothelium and plasma when administered orally. Objectives of the present study were to determine if similar evidence of absorption could be observed with oral reviparin sodium. Thrombosis incidence was determined 4 h after application of 10% formalin in methanol to the exposed jugular vein. A dose-dependent antithrombotic effect was observed when 0.01 to 7.5 mg/kg (20 rats/group) was administered by stomach tube immediately following thrombus initiation. Thrombotic incidence was also significantly reduced when 0.025 mg/kg was given 4 and 2 h prior to, immediately after, and 2 and 3 h following thrombus initiation. Reviparin was recovered from endothelium and plasma in trace amounts at all doses. At 0.025 mg/kg, peak aortic endothelial reviparin concentrations were found at 1 and 2 h and peak plasma anti-Xa activity was detected at 2 h. Trace amounts of plasma TFPI were found only at 8 h after administration. Dose-dependent antithrombotic activity and recovery from endothelium and plasma support the hypothesis that orally administered reviparin sodium is absorbed.

Keywords

Reviparin sodium - thrombosis - oral - rats

Full Text

References

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