In vitro flow cytometry method to quantitatively assess inhibitors of P-glycoprotein.
Drug Metab Dispos
; 28(5): 522-8, 2000 May.
Article
en En
| MEDLINE
| ID: mdl-10772630
P-glycoprotein (Pgp)-mediated drug efflux is a major factor contributing to the variance of absorption and distribution of many drugs. 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 alpha-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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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Subfamilia B de Transportador de Casetes de Unión a ATP
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Drug Metab Dispos
Asunto de la revista:
FARMACOLOGIA
Año:
2000
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos