AGE-DEPENDENT INTESTINAL HYDROLYSIS OF VALPROATE GLUCURONIDE IN RAT

1. Age-dependent differences in the intestinal hydrolysis of the glucu ronide conjugate of valproic acid were evaluated in the Fischer-344 ra t at 14 and 40 days, and 24 months of age. 2. Hydrolysis occurred more quickly when incubations were conducted under anaerobic as compared w ith aerobic conditions. 3. The rate of hydrolysis of valproate glucuro nide was most rapid in the contents of the large intestine (caecum and colon); no difference in rate was noted between age groups during inc ubations with large intestinal contents. 4. Hydrolysis in the tissues of the large and small intestines, and the contents of the small intes tine, was more rapid in the 14-day-old rat than in the older age group s. Differences in the rates and sites of hydrolysis in the 14-day-old animal may be due to regional differences in the number and types of m icroorganisms or mammalian beta-glucuronidase present in the gastroint estinal tract. 5. Differences in intestinal hydrolysis of valproate gl ucuronide may account in part for age-related changes in enterohepatic recirculation of valproate in young animals; other mechanisms apparen tly are responsible for altered valproate disposition in senescent ani mals.