Influence of methylxanthine-containing foods on theophylline metabolism and kinetics.
The metabolism and kinetics of 14C-labeled theophylline have been studied after intravenous doses of 100 mg to 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 has also been investigated. Metabolites were separated and quantitated by ion-exchange column chromatography, ion-exchange paper chromatography, and liquid scintillation counting. Three major metabolites were found in urine in addition to theophylline, namely 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 intravenous administration; theophylline, 1,3-dimethyluric acid, and 1-methyluric acid were eliminated by first-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 to 7.0 hr (p less than 0.02) due to increases 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 table form, kinetics and metabolism of theophylline were the same as in subjects on usual diets.
D000284:Administration, Oral; D000328:Adult; D004032:Diet; D006801:Humans; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D013806:Theophylline / Q000008:administration & dosage / Q000378:metabolism* / Q000652:urine; D014527:Uric Acid / Q000652:urine; D014970:Xanthines / Q000378:metabolism* / Q000652:urine
D014970:Xanthines; D014527:Uric Acid; C008514:methylxanthine; D013806:Theophylline