Early inhibition of hepatic bilirubin conjugation after paracetamol (acetaminophen) administration in the rat

Abstract

Administration of paracetamol (acetaminophen) 13.3 mmol kg-1 body weight to rats led 2 h later to an impaired capacity to conjugate an intravenous load of bilirubin, in the absence of biochemical signs of liver damage and before the reactive metabolite of the drug had become bound within the liver. In addition, paracetamol inhibited the excretion into the bile of conjugated bilirubin, although the plasma levels of the uncomjugated pigment only were elevated. This study provides additional evidence that hepatic glucuronide conjugation is impaired early after paracetamol overdose, and that this precedes the accumulation and binding of the hepatotoxic metabolite of the drug within the liver cells.