Ls. Gan et al., USE OF CACO-2 CELLS AS AN IN-VITRO INTESTINAL-ABSORPTION AND METABOLISM MODEL, Drug development and industrial pharmacy, 20(4), 1994, pp. 615-631
The Caco-2 cell line, a human colorectal carcinoma cell line, is an es
tablished in vitro model for the study of drug transport in the human
intestine. We have routinely utilized this in vitro model to 1) elucid
ate intestinal absorption mechanisms of small drug molecules and pepti
de-like therapeutic agents (e.g. paracellular/transcellular passive di
ffusion and carrier-mediated active transport), 2) screen and select o
rally active therapeutic agents, 3) identify optimum luminal pH's for
drug absorptions, 4) address dissolution rate-related absorption probl
ems, 5) assess mucosal toxicity of therapeutic agents, and 6) evaluate
prodrug approaches for enhanced drug absorptions. We have also utiliz
ed this in vitro model to assess the metabolic stability of therapeuti
c agents in the intestinal epithelium. Demonstrated in this report are
primarily the techniques for the elucidation of absorption mechanisms
. Examples of the characterization of paracellular/transcellular passi
ve diffusion pathways and carrier-mediated active transport will be gi
ven. Application of the Caco-2 model to the process of drug developmen
t will also be discussed.