Tissue distribution of caffeine and its metabolites in the mouse

The disposition of a single oral dose of 5 or 25 mg/kg of [3H, 14C]caffeine in the brain, heart, kidneys, liver, lungs, spleen, testes, muscle, plasma and erythrocytes of the CD-1 mouse was investigated. Caffeine appeared in all tisues within 5 min. It distributed in proportion to tissue water only at 1 hr after dosing, entering and leaving various organs at different rates. The maximum organ half-life of caffeine was 3 hr. A shorter half-life was observed after the 5-mg/kg dose, but the disposition of both doses was otherwise similar. 1,7-Dimethylxanthine is the major tissue metabolite. Little methyluric acid was present in the tissues. No methylxanthine nucleotides were demonstrable in the liver. The exposure of organs to caffeine and 1,7-dimethylxanthine was calculated.