Human disposition and some biochemical aspects of methylxanthines

The human disposition of caffeine, theophylline, and theobromine is essentially characterized by rapid and complete gastrointestinal absorption; minimal first pass metabolism; distribution throughout the total body water; extensive and, in the case of caffeine almost complete, biotransformation in the liver; and elimination of metabolites from the body via the kidneys. Methylxanthine metabolism is affected by such factors as diet, smoking, pregnancy, use of oral contraceptives, age, and disease state. These factors have been studied extensively in relationship to caffeine disposition, less so for theophylline, and minimally for theobromine as well as the metabolites of these compounds, in particular paraxanthine and the diaminouracils. The facts that the loss of the 3-methyl group from caffeine to form 1,7-dimethylxanthine (paraxanthine) is the preferential path of metabolism in humans and that an acetylated diaminouracil is one of the major end-products of caffeine metabolism would indicate the need for additional studies of these compounds. The variability often associated with caffeine disposition may be in part genetic in origin since the population is generally biomodally distributed in its ability to acetylate molecules possessing an amino functional group. In addition, caffeine metabolism may be useful as a diagnostic tool to determine an individual's ability to acetylate and thus eliminate potentially harmful compounds from the body, as well as a measure of liver function in terms of enzymatic metabolizing ability.