Antithrombotic activity of orally administered low molecular weight heparin (Logiparin) in a rat model

Previous studies in rats demonstrated that orally administered, unfractiona ted bovine lung heparin is absorbed and has a dose-dependent antithrombotic effect. The objective of this study was to determine if an oral low molecu lar weight heparin had a similar antithrombotic effect in the same model. T hrombosis was induced in rats by application of 10% formalin in 65% methano l to the exposed jugular vein. Immediately following, saline, unfractionate d 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 Lo giparin reduced the incidence of thrombosis at all doses with a dose-depend ent effect suggested. A significant increase was observed in the activated partial thromboplastin time and in plasma heparin concentrations, determine d by Accuclot(TM) Heptest(R) and anti-factor Xa chromogenic assay for rats given oral Logiparin versus saline. A dose-dependent increase in plasma hep arin concentration was observed when estimated by the anti-Xa chromogenic a ssay. Heparin was recovered in 9% of aortic endothelial samples when greate r than or equal to0.8 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 fo r unfractionated bovine lung heparin indicating that oral Logiparin is an e ffective antithrombotic agent at doses lower than unfractionated heparin. O rally administered low molecular weight heparin may be useful for the preve ntion a nd treatment of thrombosis. Copyright (C) 2001 S. Karger AG, Basel.