Leone-Bay A, Paton D R, Freeman J, Lercara C, O'Toole D, Gschneidner D, Wang E, Harris E, Rosado C, Rivera T, DeVincent A, Tai M, Mercogliano F, Agarwal R, Leipold H, Baughman R A
Emisphere Technologies, Inc., Hawthorne, New York 10532, USA.
J Med Chem. 1998 Mar 26;41(7):1163-71. doi: 10.1021/jm970811m.
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.
已发现一类新型化合物（递送剂），可促进大鼠和灵长类动物对美国药典肝素的胃肠道吸收。将这些递送剂与肝素联合，以丙二醇水溶液的形式口服或结肠内给药，可使血浆肝素浓度（抗Xa因子）和凝血时间（活化部分凝血活酶时间）显著增加。使用该系列中最有效的一种递送剂，食蟹猴口服给药后估计相对生物利用度可达8%。为建立体内数据与体外参数之间的相关性，进行了固定化人工膜（IAM）色谱分析。对数相对k'值与口服肝素递送效率相关。
