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• W2127976260 abstract "Membrane transporters can play a clinically important role in drug absorption and disposition; Caco-2 and Madin-Darby canine kidney (MDCK) cells are the most widely used in vitro models for studying the functions of these transporters and associated drug interactions. Transport studies using these cell models are mostly focused on apical transporters, whereas basolateral drug transport processes are largely ignored. However, for some hydrophilic drugs, a basolateral uptake transporter may be required for drugs to enter cells before they can interact with apical efflux transporters. The objective of this study was to evaluate potential differences in drug transport across Caco-2 and MDCK basolateral membrane that could cause discrepancy in the identification of efflux transporter substrates and to elucidate the underlying factors that may cause such differences, using rosuvastatin as a model substrate. Bidirectional transport results in Caco-2 and breast cancer resistance protein-MDCK cells demonstrated the necessity of an uptake transporter at the basolateral membrane for rosuvastatin. Kinetic study revealed saturable and nonsaturable processes for rosuvastatin uptake across the Caco-2 basolateral membrane, with the saturable process encompassing >75% of overall rosuvastatin basolateral uptake at concentrations below the <i>K</i>_m (4.2 μM). Furthermore, rosuvastatin basolateral transport exhibited <i>cis</i>-inhibition and <i>trans</i>-stimulation phenomena, indicating a facilitated diffusion mechanism. This basolateral transporter appeared to be a prerequisite for rosuvastatin and perhaps for other hydrophilic substrates to interact with apical efflux transporters. Deficit of such a basolateral transporter in certain cell models may lead to false-negative results when screening drug interactions with apical efflux transporters." @default.
• W2127976260 created "2016-06-24" @default.
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• W2127976260 date "2012-08-01" @default.
• W2127976260 modified "2023-10-10" @default.
• W2127976260 title "The Role of a Basolateral Transporter in Rosuvastatin Transport and Its Interplay with Apical Breast Cancer Resistance Protein in Polarized Cell Monolayer Systems" @default.
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• W2127976260 doi "https://doi.org/10.1124/dmd.112.045666" @default.
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