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- W2079484522 abstract "The hypothesis that higher molecular weight (MW) quaternary ammoniums (QAs) form lipophilic ion-pair complexes with bile salts in the liver, and are subsequently excreted into bile via a canalicular transporter, P-gp, was re-examined in the present study for its validity. The biliary excretion of tributylmethyl ammonium (TBuMA), a QA with a MW of 200, in bile salt-depleted rats was determined. Depletion was induced by a daily oral administration of a resin, cholestyramine, at a dose of 0.5 g/kg for 2 consecutive weeks, which decreased the concentration of total bile salts in the liver by 38%. When TBuMA was administered intravenously (12 µmol/kg) to these rats, the plasma level, area under the plasma concentration-time curve (AUC), systemic clearance (CL) and volume of distribution (Vss) of the compound remained unchanged, whereas bile flow (23.03 vs 16.94 µl/min, p<0.05) and biliary clearance (CLbile, 12.75 vs 5.34 ml/min/kg, p<0.01) were decreased significantly. These results implied the biliary clearance of TBuMA in rats with bile salt depletion was significantly decreased as a result of decreased ion-pair complexation of TBuMA. The above results are consistent with our hypothesis and the existence of a MW threshold (i.e. 200±50 for rats) for the biliary excretion of QAs. Copyright © 2007 John Wiley & Sons, Ltd." @default.
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- W2079484522 date "2007-01-01" @default.
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- W2079484522 title "Decreased biliary excretion of tributylmethyl ammonium in cholestyramine pretreated rats due to reduced formation of ion-pair complexes with hepatic bile salts" @default.
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- W2079484522 doi "https://doi.org/10.1002/bdd.580" @default.
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