Background: Drug transporters function as gatekeepers and modulate drug access into body
and various tissues. Thus, a thorough and precise understanding of transporter liability for compound
uptake and efflux is critical during drug development.
Methods: In the present study, we assessed the apparent permeability (Papp) and compared efflux ratio
of various compounds in stably transfected Madin-Darby Canine Kidney (MDCKII) cells overexpressing
human P-gp (MDCKII-MDR1), human BCRP (MDCKII-BCRP), wild-type (MDCKII-WT), and
Caco-2 cell monolayers.
Results: We observed that quinidine, a substrate for MDR1 transporter, showed efflux ratio (Papp B-A/
Papp A-B) of 838 in MDCKII-MDR1 cells which plummeted to 14 in presence of verapamil, a known
inhibitor of MDR1. With MDCKII-WT cells, Papp of quinidine dropped from 2 to 1, in the presence of
verapamil. Caco-2 cells showed a diminutive decrease in efflux ratio of quinidine from 2.5 to 1.6 by
verapamil. Prazosin and dantrolene were evaluated in MDCKII-BCRP cells and were found to have
80-fold higher efflux ratio compared to MDCKII-WT cells. In Caco-2 cells, prazosin and dantrolene
showed efflux ratio of 4 and 2, respectively. Rhodamine-123, a fluorogenic probe substrate of MDR1
showed an efflux ratio of 4 in Caco-2 cells and BCRP substrate estrone-3-sulphate showed an efflux
ratio of 7. In presence of BCRP inhibitor fumitremorgin-c, the efflux ratio of estrone-3-sulfate dropped
to 1 in Caco-2 cells.
Conclusion: The very high efflux ratios of MDR1 and BCRP substrates in transfected MDCKII cells
clearly demonstrate the potential usefulness of these models to provide more definitive data to evaluate
the transporter involvement compared to Caco-2 or MDCKII-WT cells.