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• W2121102751 abstract "In the present study, we examined in vitro biliary clearance of several compounds in sandwich-cultured rat hepatocytes (SCRH) and compared it with that observed in vivo in rats; the effect of plasma protein binding on in vitro-in vivo correlation of biliary excretion was also assessed. The in vitro biliary excretion was determined by differential cumulative uptake of compounds in SCRH preincubated in the presence and absence of Ca²⁺/Mg²⁺. The cumulative uptake study of radiolabeled substrates revealed that the function of canalicular efflux transporters such as bile salt export pump, multidrug resistance-associated protein 2, breast cancer resistance protein, and multidrug resistance 1 was adequately maintained in SCRH. Unlabeled test compounds, pravastatin, rosuvastatin, valsartan, cefmetazole, and cefoperazone exhibited varying degrees of in vitro biliary excretion in the cumulative uptake study using SCRH. In vivo biliary excretions of these compounds were measured in common bile duct-cannulated rats. Whereas their biliary excretion ratios were all more than 60% of the dose, the in vivo intrinsic biliary clearances varied from 10.5 to 1787.2 ml/min/kg. The in vitro intrinsic biliary clearances of test compounds were well correlated with their corresponding in vivo intrinsic clearances calculated on the basis of the plasma unbound concentration (<i>r</i>² = 0.984), whereas less correlation was observed when they were calculated on the basis of plasma total concentration (<i>r</i>² = 0.217). These results indicate that SCRH is a useful in vitro model for predicting in vivo intrinsic biliary clearance in rats. In addition, for an accurate prediction, it is necessary to evaluate the in vivo intrinsic biliary clearance based on plasma unbound concentration but not total concentration." @default.
• W2121102751 created "2016-06-24" @default.
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• W2121102751 date "2008-04-03" @default.
• W2121102751 modified "2023-09-26" @default.
• W2121102751 title "Effect of Plasma Protein Binding on in Vitro-in Vivo Correlation of Biliary Excretion of Drugs Evaluated by Sandwich-Cultured Rat Hepatocytes" @default.
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• W2121102751 doi "https://doi.org/10.1124/dmd.107.019026" @default.
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