Dose-Dependent Biliary and Renal Excretion of Paracetamol in the Rat

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Abstract
In rats, the biliary and renal excretion of paracetamol changed in a dose-dependent manner. After an oral nonhepatotoxic dose of 200 mg/kg paracetamol, the drug excreted in the bile amounted to only 5.5% within 24 h, whereas 72% of the dose were excreted into the urine. Following an oral hepatotoxic dose (1,000 mg/kg), the biliary excretion of total paracetamol was enhanced to 13.5% whereas the renal elimination was reduced to 51% of the dose. After a nontoxic intravenous treatment with paracetamol (25–100–400 mg/kg), both the excretion of paracetamol conjugates into the bile and the elimination of free paracetamol into the urine were augmented in a dose-dependent manner. Hepatic damage due to carbon tetrachloride pretreatment (0.5 ml/kg i.p. 24 h before 100 mg/kg paracetamol i.v.) diminished both the bile flow and the biliary excretion of paracetamol conjugates, whereas the renal elimination was not affected.

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