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 (Papp) values of 55 compounds with known human absorption values were determined using MDCK cell monolayers. For comparison, Papp 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-microm 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 microM donor solutions in transport medium (pH 7.4) containing 1% DMSO. The Papp values in MDCK cells correlated well with those in Caco-2 cells (r2 = 0.79). Spearman's rank correlation coefficient for MDCK Papp and human absorption was 0.58 compared with 0.54 for Caco-2 Papp and human absorption. These results indicate that MDCK cells may be a useful tool for rapid membrane permeability screening.
Irvine
J D
JD
Affymax Research Institute (a Glaxo Wellcome Company), Santa Clara, California 95051, USA.jennifer_irvine@affymax.com
Takahashi
L
L
Lockhart
K
K
Cheong
J
J
Tolan
J W
JW
Selick
H E
HE
Grove
J R
JR
D000465:Algorithms; D000818:Animals; D001692:Biological Transport; D018938:Caco-2 Cells; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000502:physiology*; D004285:Dogs; D006801:Humans; D007408:Intestinal Absorption; D007668:Kidney / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D011786:Quality Control