INFLUENCE OF METHYLXANTHINE-CONTAINING FOODS ON THEOPHYLLINE METABOLISM AND KINETICS

The metabolism and kinetics of 14C-labeled theophylline were studied after i.v. doses of 100 mg of healthy subjects, keeping to their usual diets after 7 days of abstention from methylxanthine-containing foods and beverages and again after such abstention while taking caffeine and theophylline in tablet form. The metabolism of oral 14C-theophylline was studied. Metabolites were separated and quantitated by ion-exchange column chromatography, ion-exchange paper chromatography and liquid scintillation counting. Theophylline and 3 major metabolites were found in urine; 3-methylxanthine, 1,3-dimethyluric acid and 1-methyluric acid, and 2 minor metabolites were detected but not identified. The elimination kinetics were studied after i.v. administration. Theophylline, 1,3-dimethyluric acid and 1-methyluric acid were eliminated by 1st-order processes, while elimination of 3-methylxanthine was described by Michaelis-Menten kinetics. Abstention from methylxanthine-containing foods and beverages led to a significant decrease in the urinary elimination half-life of 14C from 9.8-7.0 h (P < 0.02) due to increase in the elimination constants for theophylline, 3-methylxanthine and 1,3-dimethyluric acid. When the methylxanthine content of the methylxanthine-containing foods and beverages was replaced by caffeine and theophylline in tablet form, kinetics and theophylline metabolism were the same as in subjects on usual diets.