Urinary metabolites of caffeine in young dogs.

Urinary elimination of [1-methyl-14C]caffeine was investigated in young dogs. Mongrel dogs aged 2 days, 1 week, and 5 weeks received single doses of caffeine (50 mg/kg) through an orogastric tube. Eight dogs, each studied once, were involved. At identical times after the dose the ratio of urinary caffeine metabolites to unchanged caffeine was greatest in the 5-week-old and smallest in the 2-day-old puppy; cumulative ratios at (or very close to) the plateau of urinary excretion varied between 8.7 and 17.8 in the 5-week-old, 3.6 and 3.8 in the 1-week-old, and 2.2 and 2.4 in the 2-day-old dogs. The time needed to reach the plateau of the cumulative excretion of radioactivity in the urine decreased with age. Initially only caffeine was detected in the urine of the 2-day-old and 1-week-old dogs; the first quantitatively important metabolites were trimethyluric acid and 6-amino-5-(N-methylformylamino)-1,3 dimethyluracil (also known as 1,3,7-trimethyldihydrouric acid) in the 2-day-old, and the uracil derivative and theophylline in the 1-week-old and the 5-week-old puppies. The percentage of demethylated uric acid metabolites and uracil derivatives increased progressively with increasing age; this indicates increased demethylation, oxidation to uric acids and hydrolysis of the imidazole ring of caffeine with increasing age. These results are consistent with the previously reported slow plasma elimination of caffeine in the newborn and confirm the limited capacity of the young (as compared to the adult) mammal to metabolize caffeine.