SYNTHESIS AND EVALUATION OF COMPOUNDS THAT FACILITATE THE GASTROINTESTINAL ABSORPTION OF HEPARIN

A family of novel compounds (delivery agents) that promote the gastroi ntestinal absorption of USP heparin in rats and primates has been disc overed. The delivery agents in combination with heparin were administe red either orally or intracolonically in an aqueous propylene glycol s olution and caused dramatic increases in both plasma heparin concentra tions (anti-Factor Xa) and clotting times (APTT). Using one of the mos t effective delivery agents in this series, an estimated relative bioa vailability of 8% can be achieved following oral administration to cyn omolgus monkeys. To establish a correlation between the in vivo data a nd an in vitro parameter, immobilized artificial membrane (IAM) chroma tography was performed. Log relative k' values were correlated to the efficiency of oral heparin delivery.