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

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.