The antithrombotic
drug heparin is administered parenterally and believed not effective orally. Oral
heparin would be most suitable for long term administration, often required for the prevention of
thrombosis. Following parenteral administration,
heparin is taken up by endothelial cells. Our laboratory has shown that
heparin is similarly taken up by endothelium following
oral administration, despite low plasma
heparin concentrations. In a twenty-four hour period, endothelial
heparin concentrations are greatest within 15 minutes of oral dosing although plasma levels never exceed one percent of dose. Endothelial uptake accounts for a considerable amount of absorption if the total body endothelium is considered. In support of oral
heparin absorption, we demonstrated a dose-dependent decrease in
thrombosis incidence in a rat jugular vein model following single oral doses of unfractionated heparins (bovine and porcine) or low molecular weight heparins (
reviparin,
logiparin and
ardeparin). Low molecular weight heparins were effective at lower doses than unfractionated heparins where a fifty percent reduction in
thrombosis was observed with 0.025 mg/kg
reviparin, 0.1 mg/kg
logiparin, versus 7.5 mg/kg bovine
unfractionated heparin. These studies support the work of others demonstrating measurable systemic changes following oral
heparin administration and suggest that
heparin may be effective when administered by the oral route. It also indicates that the presence of
heparin in plasma likely reflects a much greater amount associated with endothelium.