TY - JOUR T1 - In Vitro Flow Cytometry Method to Quantitatively Assess Inhibitors of P-Glycoprotein JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 522 LP - 528 VL - 28 IS - 5 AU - Er-jia Wang AU - Christopher N. Casciano AU - Robert P. Clement AU - William W. Johnson Y1 - 2000/05/01 UR - http://dmd.aspetjournals.org/content/28/5/522.abstract N2 - 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 α-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. The American Society for Pharmacology and Experimental Therapeutics ER -