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Pharmaceutics 2016, 8(2), 12;

Evaluation of P-Glycoprotein Inhibitory Potential Using a Rhodamine 123 Accumulation Assay

Institut de Recherches en Santé, Environnement et Travail (IRSET), UMR INSERM U1085, Faculté de Pharmacie, 2 Avenue du Pr Léon Bernard, 35043 Rennes, France
Centre de Pharmacocinétique, Technologie Servier, 25-27 Rue Eugène Vignat, 45000 Orléans, France
Pôle Biologie, Centre Hospitalier Universitaire, 2 rue Henri le Guilloux, 35033 Rennes, France
Author to whom correspondence should be addressed.
Academic Editor: Yvonne Perrie
Received: 26 January 2016 / Revised: 22 March 2016 / Accepted: 6 April 2016 / Published: 12 April 2016
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In vitro evaluation of P-glycoprotein (P-gp) inhibitory potential is now a regulatory issue during drug development, in order to predict clinical inhibition of P-gp and subsequent drug–drug interactions. Assays for this purpose, commonly based on P-gp-expressing cell lines and digoxin as a reference P-gp substrate probe, unfortunately exhibit high variability, raising thus the question of developing alternative or complementary tests for measuring inhibition of P-gp activity. In this context, the present study was designed to investigate the use of the fluorescent dye rhodamine 123 as a reference P-gp substrate probe for characterizing P-gp inhibitory potential of 16 structurally-unrelated drugs known to interact with P-gp. 14/16 of these P-gp inhibitors were found to increase rhodamine 123 accumulation in P-gp-overexpressing MCF7R cells, thus allowing the determination of their P-gp inhibitory potential, i.e., their half maximal inhibitor concentration (IC50) value towards P-gp-mediated transport of the dye. These IC50 values were in the range of variability of previously reported IC50 for P-gp and can be used for the prediction of clinical P-gp inhibition according to Food and Drug Administration (FDA) criteria, with notable sensitivity (80%). Therefore, the data demonstrated the feasibility of the use of rhodamine 123 for evaluating the P-gp inhibitory potential of drugs. View Full-Text
Keywords: P-glycoprotein; inhibition; drug–drug interactions; rhodamine 123; digoxin P-glycoprotein; inhibition; drug–drug interactions; rhodamine 123; digoxin

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Jouan, E.; Le Vée, M.; Mayati, A.; Denizot, C.; Parmentier, Y.; Fardel, O. Evaluation of P-Glycoprotein Inhibitory Potential Using a Rhodamine 123 Accumulation Assay. Pharmaceutics 2016, 8, 12.

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