TY - JOUR T1 - Age-related changes in the disposition of benzyl acetate. A model compound for glycine conjugation. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 506 LP - 512 VL - 17 IS - 5 AU - T F McMahon AU - J J Diliberto AU - L S Birnbaum Y1 - 1989/09/01 UR - http://dmd.aspetjournals.org/content/17/5/506.abstract N2 - The in vivo metabolism and excretion of benzyl acetate (BA), a model compound for glycine conjugation, was examined in male Fischer 344 rats and C57BL/6N mice. Rats aged 3-4, 9, and 25 months received a single oral dose of either 5 or 500 mg/kg 14C-BA, while male mice aged 2, 13, and 25 months received a single oral dose of 10 mg/kg 14C-BA. Urine and feces were collected for 96 hr. Biliary excretion and plasma elimination were also examined in male Fischer rats after iv administration of 5 mg/kg 14C-BA. In both young and old rats and mice, hippuric acid (HA) was the major urinary metabolite after oral dosing of BA. No significant age-related difference was observed in rats in the urinary elimination of BA-derived radioactivity or in the percentage of the total dose excreted as hippuric acid (approximately 95%). Twenty-five-month old rats excreted a significantly higher percentage of the total dose as benzyl mercapturic acid (approximately 2%) than did 3- to 4-month-old rats (approximately 1%) at the 5 mg dose. Benzyl mercapturic acid excretion in 3- to 4-month-old rats was also increased significantly at 500 mg/kg BA vs. 5 mg/kg BA. Fecal excretion of BA-derived radioactivity declined significantly in 25-month-old rats at both the 5 and 500 mg dose. This decrease was reflected by an age-related decline in biliary excretion and higher plasma levels of BA-derived radioactivity. Examination of plasma metabolites revealed a significantly higher level of HA and benzoyl glucuronide in 25-month rats.(ABSTRACT TRUNCATED AT 250 WORDS) ER -