USE OF CACO-2 CELLS AS AN IN-VITRO INTESTINAL-ABSORPTION AND METABOLISM MODEL

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.