title: Implementation of the caco-2 cell culture model as a predictive tool for the oral absorption of drugs. In-house evaluation procedures.
abstract: The Caco-2 cell culture model is widely used during drug development and lead optimization as a predictive tool for the oral absorption of drugs. In order to improve the reliability and quality of the results of Caco-2 experiments and to ensure that the system being used is functionally and enzymatically representative for the intestinal mucosa, it is important to perform a validation of the implemented Caco-2 system. In this paper, we summarize evaluation techniques to guarantee the in-house validity of the model. Theophyllin and sodium fluorescein are used as model compounds to evaluate passive transcellular and passive paracellular transport, respectively. Phenylalanine serves as a substrate to demonstrate active carrier mechanisms. Aminopeptidase and dipeptidyl peptidase are two brush border enzymes present in an active form in the Caco-2 culture model. The presence of an active efflux carrier mechanism is demonstrated with cyclosporin A as a substrate.
authors.affiliation: Biopharmaceutics & Drug Delivery, Lilly Development Centre, Mont-Saint-Guibert, Belgium.
authors.forename: F
authors.initials: F
authors.lastname: Ingels
authors.forename: S
authors.initials: S
authors.lastname: Deferme
authors.forename: N
authors.initials: N
authors.lastname: Delbar
authors.forename: M
authors.initials: M
authors.lastname: Oth
authors.forename: P
authors.initials: P
authors.lastname: Augustijns
mesh_terms: D018938:Caco-2 Cells / Q000502:physiology*; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011237:Predictive Value of Tests
chemical_list: D004364:Pharmaceutical Preparations