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Vol. 28, Issue 5, 522-528, May 2000
Department of Drug Metabolism and Pharmacokinetics, Schering-Plough
Research Institute, Lafayette, New Jersey
P-glycoprotein (Pgp)-mediated drug efflux is a major factor
contributing to the variance of absorption and distribution of many
drugs (Hall et al., 1999). A simple and reliable in vitro method to
identify inhibitors of Pgp helps to prevent the potential of drug
interactions. Using daunorubicin as a fluorescent marker and vanadate
as a positive control compound, a functional flow cytometry method for
assessing the ability of a drug to inhibit Pgp-mediated drug efflux
from CR1R12 multidrug-resistant cells has been evaluated. Quantitation
of the relative fluorescence was used to compare potency of individual
inhibitors. Known Pgp inhibitors, such as cyclosporin A, nicardipine,
verapamil, quinidine, terfenadine, tamoxifen, and vinblastine were
demonstrated to inhibit the Pgp-mediated efflux of daunorubicin.
Cyclosporin A and terfenadine were the most potent inhibitors among the
compounds tested. Tetraphenylphosphonium and 
-tocopherol had little
inhibitory effect. Progesterone produced significant inhibition at
relatively high concentrations. This study demonstrated
that this in vitro flow cytometry method is a simple, sensitive, and
quantitative tool to assess the capacity of a drug to inhibit Pgp
transporters, and is useful for screening or identifying inhibitors of
Pgp as well as evaluation of potential for drug interactions.
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