The effect of prolonged sodium phenobarbitone treatment on hepatic xenobiotic metabolism and the urinary excretion of metabolites of the d-glucuronic acid pathway in the rat

Male Sprague-Dawley rats were fed a 0.1 % (w/w) sodium phenobarbitone (PB) diet for periods of 4, 12 and 24 weeks. Phenobarbitone treatment resulted in a marked increase in liver size which was accompanied by the induction of several parameters of hepatic xenobiotic metabolism including mixed function oxidase enzyme activities, UDP-glucuronyltransferase, cytochrome P450 and the microsomal protein content. In addition, treatment with the barbiturate led to the stimulation of the urinary excretion of d-glucaric acid, l-gulonic acid, free d-glucuronic acid, l-ascorbic acid and xylitol. The levels of stimulation of both the hepatic and urinary parameters remained relatively constant throughout the period of treatment. On cessation of PB treatment the parameters of hepatic xenobiotic metabolism reverted to control levels at a faster rate than the excretion of the d-glucuronic acid metabolites. The results demonstrate a correlation between the urinary excretion of metabolites of the d-glucuronic acid pathway and hepatic xenobiotic metabolizing enzyme activities during the prolonged administration of PB.