Antithrombotic efficacy in a rat model of the low molecular weight heparin, reviparin sodium, administered by the oral route

Previous studies in rats shaw that unfractionated heparin and the low molec ular weight heparin logiparin have a dose-dependent antithrombotic effect a nd are found in endothelium and plasma when administered orally. Objectives of the present study were to determine if similar evidence of absorption c ould be observed with oral reviparin sodium. Thrombosis incidence was deter mined 4 h after application of 10% formalin in methanol to the exposed jugu lar 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 foll owing thrombus initiation. Thrombotic incidence was also significantly redu ced 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 endoth elium 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 plas ma anti-Xa activity was detected at 2 h. Trace amounts of plasma TFPI were found only at 8 h after administration. Dose-dependent antithrombotic activ ity and recovery from endothelium and plasma support the hypothesis that or ally administered reviparin sodium is absorbed.