Author: Gonzalez-Alvarez I., Navarro-Fontestad C., Fernandez-Teruel C.(1), Merino V., Bermejo M, University of Valencia.
Names and affiliation of other authors:
Oral or poster: Poster
The aim of this study is to compare the differences between several cell lines (CaCo-2, TC7, MDCK, MDCK-MDR1), for this propose we studied the absorption of celiprolol, a known P-glycoprotein substrate, in those cell lines.
CaCo-2 and TC7 cells grew in a collagen coated polycarbonate membrane until confluence during 19-22 days and MDCK and MDCK-MDR1 grew until confluence during 5-7 days. Permeability studies were conducted in Hank’s balance solution (pH=7.00) at 37ºC and 50 oscillations/min. The integrity of the monolayer was evaluated by measure of the trans-epithelial electrical resistance (TEER). The donor drug concentration ranged from 21 M to 4200 M. Transport studies were performed in both directions, from apical-to-basolateral (A-to-B) and from basolateral-to-apical (B-to-A).
The in vitro experiments showed significant differences between A-to-B and B-to-A permeabilities (p<0.05) and also a concentration-dependent permeation process. The analysis of A-to-B and B-to-A permeabilities suggested the existence of an efflux mechanism.
The future objective is to compare this data with data obtained in other laboratory (Novonordisk) and to correlate the Peff with the expression of P-gp expressed in each cell line (experiments will be done by Solvo)