THE USE OF THE INTESTINAL EPITHELIAL-CELL CULTURE MODEL, CACO-2, IN PHARMACEUTICAL DEVELOPMENT

The need for more innovative and readily orally bioavailable therapeut ics that can be developed faster has driven the development of tools a nd strategies that will have a major impact on those needs. The applic ation of the Caco-2 human epithelial cell line for use as a tissue cul ture model for permeability measurements that can be used to predict o ral absorption effectively demonstrates this strategy. This article di scusses some applications of the Caco-2 tissue culture model in pharma ceutical development. The development of an experimental program to ch aracterize the endogenous gut peptide transport system is described, a s well as its application to the understanding of the oral absorption of cephalosporin molecules. Other studies describe the use of permeabi lity studies for a chemical series of drug candidates to predict their oral absorption in vivo. Finally, the application of the model to aid in the development of formulation strategies is discussed.