title: In Situ Perfusion Model in Rat Colon for Drug Absorption Studies: Comparison with Small Intestine and Caco-2 Cell Model.
abstract: Our aim is to develop and to validate the in situ closed loop perfusion method in rat colon and to compare with small intestine and Caco-2 cell models. Correlations with human oral fraction absorbed (Fa) and human colon fraction absorbed (Fa_colon) were developed to check the applicability of the rat colon model for controlled release (CR) drug screening. Sixteen model drugs were selected and their permeabilities assessed in rat small intestine and colon, and in Caco-2 monolayers. Correlations between colon/intestine/Caco-2 permeabilities versus human Fa and human Fa_colon have been explored to check model predictability and to apply a BCS approach in order to propose a cut off value for CR screening. Rat intestine perfusion with Doluisio's method and single-pass technique provided a similar range of permeabilities demonstrating the possibility of combining data from different laboratories. Rat colon permeability was well correlated with Caco-2 cell-4 days model reflecting a higher paracellular permeability. Rat colon permeabilities were also higher than human colon ones. In spite of the magnitude differences, a good sigmoidal relationship has been shown between rat colon permeabilities and human colon fractions absorbed, indicating that rat colon perfusion can be used for compound classification and screening of CR candidates.
authors.affiliation: Pharmacokinetics and Pharmaceutical Technology, Miguel Hernandez University, Alicante, Spain.|Pharmacokinetics and Pharmaceutical Technology, University of Valencia, Valencia, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Lozoya-Agullo
authors.affiliation: Pharmacokinetics and Pharmaceutical Technology, Miguel Hernandez University, Alicante, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: González-Álvarez
authors.affiliation: Pharmacokinetics and Pharmaceutical Technology, Miguel Hernandez University, Alicante, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: González-Álvarez
authors.affiliation: Pharmacokinetics and Pharmaceutical Technology, University of Valencia, Valencia, Spain.|Molecular Recognition and Technological Development, Polytechnic University-University of Valencia, Valencia, Spain.
authors.forename: Matilde
authors.initials: M
authors.lastname: Merino-Sanjuán
authors.affiliation: Pharmacokinetics and Pharmaceutical Technology, Miguel Hernandez University, Alicante, Spain.
authors.forename: Marival
authors.initials: M
authors.lastname: Bermejo
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D018938:Caco-2 Cells / Q000378:metabolism*; D045744:Cell Line, Tumor; D003106:Colon / Q000378:metabolism*; D003692:Delayed-Action Preparations / Q000378:metabolism; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology*; D007421:Intestine, Small / Q000378:metabolism*; D008297:Male; D023421:Models, Animal; D010477:Perfusion / Q000379:methods; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003692:Delayed-Action Preparations
keywords: Caco-2 cells; absorption; colon absorption; colonic drug delivery; fraction absorbed; in vitro models; permeability; site-specific absorption