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 o f this study was to evaluate an influence of obstructive cholestasis o n the pharmacokinetics of phenazone (antipyrine). 2 The investigation was carried out on male rabbits, randomly allocated into two groups: s ham-operated and animals with biliary ducts ligation. Phenazone was ad ministered intragastrically as a probe of drug metabolism. 3 Measureme nts, i.e. laboratory and pharmacodynamic tests, as well as pharmacokin etic 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 exa mined macro- and microscopically and biochemical analysis of the liver microsomes was performed. 4 The measured pharmacokinetic parameters s uggested an impaired biotransformation of phenazone in animals with ob structive cholestasis, leading to a slower drug elimination.