MDCK (Madin-Darby Canine Kidney) Cells: A Tool for Membrane Permeability Screening

The goal of this work was to investigate the use of MDCK (Madin–Darby canine kidney) cells as a possible tool for assessing the membrane permeability properties of early drug discovery compounds. Apparent permeability (P_app) values of 55 compounds with known human absorption values were determined using MDCK cell monolayers. For comparison, P_app values of the same compounds were also determined using Caco‐2 cells, a well‐characterized in vitro model of intestinal drug absorption. Monolayers were grown on 0.4‐µm Transwell‐COL membrane culture inserts. MDCK cells were seeded at high density and cultured for 3 days, and Caco‐2 cells were cultured under standard conditions for 21 to 25 days. Compounds were tested using 100 µM donor solutions in transport medium (pH 7.4) containing 1% DMSO. The P_app values in MDCK cells correlated well with those in Caco‐2 cells (r² = 0.79). Spearman's rank correlation coefficient for MDCK P_app and human absorption was 0.58 compared with 0.54 for Caco‐2 P_app and human absorption. These results indicate that MDCK cells may be a useful tool for rapid membrane permeability screening.