title: Synthesis and evaluation of compounds that facilitate the gastrointestinal absorption of heparin.
abstract: A family of novel compounds (delivery agents) that promote the gastrointestinal absorption of USP heparin in rats and primates has been discovered. The delivery agents in combination with heparin were administered either orally or intracolonically in an aqueous propylene glycol solution and caused dramatic increases in both plasma heparin concentrations (anti-Factor Xa) and clotting times (APTT). Using one of the most effective delivery agents in this series, an estimated relative bioavailability of 8% can be achieved following oral administration to cynomolgus monkeys. To establish a correlation between the in vivo data and an in vitro parameter, immobilized artificial membrane (IAM) chromatography was performed. Log relative k' values were correlated to the efficiency of oral heparin delivery.
authors.affiliation: Emisphere Technologies, Inc., Hawthorne, New York 10532, USA.
authors.forename: A
authors.initials: A
authors.lastname: Leone-Bay
authors.forename: D R
authors.initials: DR
authors.lastname: Paton
authors.forename: J
authors.initials: J
authors.lastname: Freeman
authors.forename: C
authors.initials: C
authors.lastname: Lercara
authors.forename: D
authors.initials: D
authors.lastname: O'Toole
authors.forename: D
authors.initials: D
authors.lastname: Gschneidner
authors.forename: E
authors.initials: E
authors.lastname: Wang
authors.forename: E
authors.initials: E
authors.lastname: Harris
authors.forename: C
authors.initials: C
authors.lastname: Rosado
authors.forename: T
authors.initials: T
authors.lastname: Rivera
authors.forename: A
authors.initials: A
authors.lastname: DeVincent
authors.forename: M
authors.initials: M
authors.lastname: Tai
authors.forename: F
authors.initials: F
authors.lastname: Mercogliano
authors.forename: R
authors.initials: R
authors.lastname: Agarwal
authors.forename: H
authors.initials: H
authors.lastname: Leipold
authors.forename: R A
authors.initials: RA
authors.lastname: Baughman
mesh_terms: D000596:Amino Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D006493:Heparin / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D008252:Macaca fascicularis; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D006493:Heparin