A. Leonebay et al., SYNTHESIS AND EVALUATION OF COMPOUNDS THAT FACILITATE THE GASTROINTESTINAL ABSORPTION OF HEPARIN, Journal of medicinal chemistry, 41(7), 1998, pp. 1163-1171
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.