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• W1994769512 abstract "Prediction of biliary excretion is a challenge for drug discovery scientists due to the lack of in vitro assays. This study explores the possibility of establishing a simple assay to predict in vivo biliary excretion via the mrp2 transport system.In vitro mrp2 activity was determined by measuring the ATP-dependent uptake of 5(6)-carboxy-2′,7′-dichlorofluorescein (CDCF) in canalicular plasma membrane vesicles (cLPM) from rat livers. The CDCF uptake was time- and concentration-dependent (Km of 2.2 ± 0.3 µM and Vmax of 115 ± 26 pmol/mg/min) and strongly inhibited by the mrp2 inhibitors, benzbromarone, MK-571, and cyclosporine A, with IC50 values ≤ 1.1 µM.Low inhibition of CDCF uptake by taurocholate (BSEP inhibitor; 57 µM) and digoxin (P-gp inhibitor; 101 µM) demonstrated assay specificity towards mrp2.A highly significant correlation (r2 = 0.959) between the in vitro IC50 values from the described mrp2 assay and in vivo biliary excretion in rats was observed using 10 literature compounds.This study demonstrated, for the first time, that a high throughput assay could be established with the capability of predicting biliary excretion in the rat using CDCF as a substrate." @default.
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• W1994769512 date "2011-10-02" @default.
• W1994769512 modified "2023-10-18" @default.
• W1994769512 title "A high throughput<i>in vitro</i>mrp2 assay to predict<i>in vivo</i>biliary excretion" @default.
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• W1994769512 doi "https://doi.org/10.3109/00498254.2011.614021" @default.
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