Influence of methylxanthine-containing foods on theophylline metabolism and kinetics

Clin Pharmacol Ther. 1979 Oct;26(4):513-24. doi: 10.1002/cpt1979264513.


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.

MeSH terms

  • Administration, Oral
  • Adult
  • Diet
  • Humans
  • Injections, Intravenous
  • Kinetics
  • Male
  • Theophylline / administration & dosage
  • Theophylline / metabolism*
  • Theophylline / urine
  • Uric Acid / urine
  • Xanthines / metabolism*
  • Xanthines / urine


  • Xanthines
  • Uric Acid
  • methylxanthine
  • Theophylline