Rubas W, Jezyk N, Grass G M
Institute of Pharmaceutical Sciences, Syntex Research, Palo Alto, California 94303.
Pharm Res. 1993 Jan;10(1):113-8. doi: 10.1023/a:1018937416447.
The in vitro permeabilities of Caco-2 monolayers and permeabilities in tissue sections from colon of monkey, rabbit, and dog were compared using a series of compounds. The selected compounds differed in their physicochemical properties, such as octanol/water partition coefficient, water solubility, and molecular weight. Their structure included steroids, carboxylic acids, xanthins, alcohols, and polyethylene glycols. A linear permeability relationship was established between Caco-2 and colon tissue from both rabbit and monkey. The results suggest that Caco-2 is twice as permeable as rabbit and five times as permeable as monkey colon. However, no clear relationship could be established between Caco-2 monolayers and dog colon permeability. A relationship between permeability in Caco-2 monolayers and human absorption was found. The results suggest that within certain limits, permeability of Caco-2 monolayers may be used as a predictive tool to estimate human drug absorption.
使用一系列化合物比较了Caco-2单层细胞的体外通透性以及猴、兔和犬结肠组织切片的通透性。所选化合物的物理化学性质各不相同，如辛醇/水分配系数、水溶性和分子量。它们的结构包括类固醇、羧酸、黄嘌呤、醇类和聚乙二醇。在Caco-2与兔和猴的结肠组织之间建立了线性通透性关系。结果表明，Caco-2的通透性是兔结肠的两倍，是猴结肠的五倍。然而，在Caco-2单层细胞与犬结肠通透性之间未能建立明确的关系。发现了Caco-2单层细胞通透性与人体吸收之间的关系。结果表明，在一定限度内，Caco-2单层细胞的通透性可作为预测人体药物吸收的工具。
