1. In unanaesthetized, freely moving rats, which displayed a circadian rhythm in bile flow, hepatic transport of dibromosulphthalein was investigated at midnight when bile flow was high and at noon when bile flow was lower. The influence of pentobarbital anaesthesia and starvation on hepatic transport of dibromosulphthalein was also studied. The influence of bile salts on the hepatic transport process was investigated by interruption of the enterohepatic circulation.
2. Maximal biliary transport of dibromosulphthalein was subject to circadian variations: the biliary transport maximum at night was 25% higher than at noon, although maximal biliary concentration was not significantly altered. The distribution volume was increased by 21% during the night, but the primary hepatic clearance constant was not changed.
3. Pentobarbital anaesthesia decreased the maximal biliary concentration and the maximal biliary excretion rate of dibromosulphthalein, but the primary hepatic clearance constant was not changed.
4. Starvation for 48 h changed the primary hepatic clearance constant as well as the biliary excretion of dibromosulphthalein.
5. Interruption of the enterohepatic circulation of bile did not change the primary hepatic clearance constant of dibromosulphthalein, but decreased biliary excretion of the drug.
6. This study clearly indicates that time of the day, feeding conditions, the use of anaesthetics and interruption of the enterohepatic circulation of bile are important determinants in biliary excretion of cholephilic dyes.
