Pharmacokinetics of phenazone (antipyrine) in rabbits with experimental common bile duct obstruction

1 An altered functional state of liver due to experimental cholestasis could result in a change in the biotransformation of drugs. The aim of this study was to evaluate an influence of obstructive cholestasis on the pharmacokinetics of phenazone (antipyrine). 2 The investigation was carried out on male rabbits, randomly allocated into two groups: sham-operated and animals with biliary ducts ligation. Phenazone was administered intragastrically as a probe of drug metabolism. 3 Measurements, i.e. laboratory and pharmacodynamic tests, as well as pharmacokinetic assays, were performed before the operation as well as 10-12 days after the bile duct ligation. At the end of the study livers were examined macro- and microscopically and biochemical analysis of the liver microsomes was performed. 4 The measured pharmacokinetic parameters suggested an impaired biotransformation of phenazone in animals with obstructive cholestasis, leading to a slower drug elimination.