Use of CACO-2 Cells as an in vitro Intestinal Absorption and Metabolism Model

Abstract

The Caco-2 cell line, a human colorectal carcinoma cell line, is an established in vitro model for the study of drug transport in the human intestine. We have routinely utilized this in vitro model to 1) elucidate intestinal absorption mechanisms of small drug molecules and peptide-like therapeutic agents (e.g. paracellular/transcellular passive diffusion and carrier-mediated active transport), 2) screen and select orally active therapeutic agents, 3) identify optimum luminal pH's for drug absorptions, 4) address dissolution rate-related absorption problems, 5) assess mucosal toxicity of therapeutic agents, and 6) evaluate prodrug approaches for enhanced drug absorptions. We have also utilized this in vitro model to assess the metabolic stability of therapeutic 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 passive diffusion pathways and carrier-mediated active transport will be given. Application of the Caco-2 model to the process of drug development will also be discussed.