Conjugation metabolism of acetaminophen and bilirubin in extrahepatic tissues of rats

An anhepatic rat model was used to explore the extrahepatic conjugating metabolism of acetaminophen and serum bilirubin. The recovery of glucuronide- and sulfate-acetaminophen was 47.5% in normal control and 13.4% in model rats in the urine collected for 6 h after administration of acetaminophen 20 mg kg(-1). Following the increase of acetaminophen dose to 150 mg kg(-1), the recovery of urinary glucuronide-acetaminophen increased by 53.9% in normal control; but it decreased by 36.4% in model rats. In contrast to normal control, the pretreatment with phenobarbital did not affect acetaminophen and its metabolite levels in plasma and urine in model rats. After the establishment of anhepatic model the serum direct bilirubin rose dramatically. Urinary bilirubin test was positive in model rats, but not in normal control. No changes were observed in serum total bilirubin and ratio of direct/total bilirubin after the pretreatment with ranitidine or phenobarbital 50 mg kg(-1), i.p. for 5 days in model rats. The results indicate that the glucuronide- and sulfate-acetaminophen formed in the extrahepatic tissues of model rats is 28.2% of normal control, serum free bilirubin can be transformed into conjugated bilirubin in extrahepatic tissues, and the regulation mechanism of phase II conjugating enzymes is different between the hepatic and extrahepatic tissues. (C) 2003 Elsevier Inc. All rights reserved.