Biliary excretion of acetaminophen in diabetic and hyperthyroid rats

In streptozotocin-induced diabetic rats the biliary excretion of total acetaminophen (AA) was reduced to 14.1% of the dose (100 mg/kg i.v.) as compared to 24.6% in controls. This was due to a significant decrease in the amounts of AA-sulfate and AA-glucuronide, whereas the AA-GSH excretion was not altered. These effects were paralleled by a marked decrease in the bile flow in diabetic rats. In hyperthyroid rats (pretreated with 0.1 mg/kg T3 for 4 days) no significant alterations in the total AA or AA-conjugate excretion into bile were observed; moreover bile flow in hyperthyroid rats was in the same range as for controls. In all, known changes in hepatic microsomal or cytosolic enzyme and cosubstrate concentrations during the diabetic or hyperthyroid state do not at all correlate with their influence on the biliary excretion of AA and its conjugates.