[Pharmacokinetics of caffeine in mice and its modification by ethanol]

In experiments on mice the pharmacokinetics (absorption, distribution, metabolism) of orally administered caffeine (18 mg/kg) using 14C caffeine as marker and the influence of simultaneously applied ethanol (1,8 g/kg) was tested. The following results were obtained: 1. Caffeine was very quickly absorbed from the gastro-intestinal tract of mice. Addition of ethanol had no noticeable influence on the absorption of caffeine. 2. The elimination of caffeine from the serum and tissues examined (liver, kidney, brain, muscle) showed an exponential course with a half life of 40-60 minutes and was completed after 4 to 5 hours. 3. By giving ethanol the elimination of caffeine was significantly decreased and its half life increased to 160-240 minutes. 4. The caffeine metabolites reached their maximal concentration in serum and tissues examined within two hours. In the liver and kidney the concentration of caffeine metabolites was greater than in the serum, whereas they were lower in the brain and muscle. At the end of the experimental the concentration of caffeine metabolites reached only very low values. 5. After administration of ethanol the caffeine metabolites were significantly decreased from the 30th to 180th minute in the liver and kidney; they were only slightly lowered in the serum and almost unchanged in the muscle and brain. The results of these experiments suggest that ethanol inhibits the metabolism of caffeine in the liver, especially by influencing its demethylation to other dimethyl- and monomethylxanthines and probably also its oxidation ot methyluric acids.