Antithrombotic activity of orally administered low molecular weight heparin (Logiparin) in a rat model.
Previous studies in rats demonstrated that orally administered, unfractionated bovine lung heparin is absorbed and has a dose-dependent antithrombotic effect. The objective of this study was to determine if an oral low molecular weight heparin had a similar antithrombotic effect in the same model. Thrombosis was induced in rats by application of 10% formalin in 65% methanol to the exposed jugular vein. Immediately following, saline, unfractionated heparin (3.3-60 mg/kg) or the low molecular weight heparin, Logiparin (0.025-15 mg/kg; 20-30 rats per group) was placed in the stomach and 4 h later the jugular vein was inspected for a thrombus. Compared to saline, oral Logiparin reduced the incidence of thrombosis at all doses with a dose-dependent effect suggested. A significant increase was observed in the activated partial thromboplastin time and in plasma heparin concentrations, determined by Accuclot Heptest and anti-factor Xa chromogenic assay for rats given oral Logiparin versus saline. A dose-dependent increase in plasma heparin concentration was observed when estimated by the anti-Xa chromogenic assay. Heparin was recovered in 9% of aortic endothelial samples when > or = 0.8 mg/kg Logiparin was administered. A 50% reduction in thrombosis was observed at 0.1 mg/kg for oral Logiparin versus 7.5 mg/kg for unfractionated bovine lung heparin indicating that oral Logiparin is an effective antithrombotic agent at doses lower than unfractionated heparin. Orally administered low molecular weight heparin may be useful for the prevention and treatment of thrombosis.
Hiebert
L M
LM
Department of Veterinary Physiological Sciences, University of Saskatchewan, Saskatoon, Canada. linda.hiebert@usask.ca
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D000284:Administration, Oral; D000818:Animals; D002417:Cattle; D004195:Disease Models, Animal; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D020246:Venous Thrombosis / Q000188:drug therapy*
D006495:Heparin, Low-Molecular-Weight