title: Comparison of the permeability characteristics of a human colonic epithelial (Caco-2) cell line to colon of rabbit, monkey, and dog intestine and human drug absorption.
abstract: 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.
authors.affiliation: Institute of Pharmaceutical Sciences, Syntex Research, Palo Alto, California 94303.
authors.forename: W
authors.initials: W
authors.lastname: Rubas
authors.forename: N
authors.initials: N
authors.lastname: Jezyk
authors.forename: G M
authors.initials: GM
authors.lastname: Grass
mesh_terms: D000818:Animals; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000502:physiology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003106:Colon / Q000166:cytology / Q000378:metabolism; D004285:Dogs; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D007422:Intestines / Q000166:cytology; D008252:Macaca fascicularis; D011817:Rabbits; D012995:Solubility; D013045:Species Specificity