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 < 0.02) due to increases in the elimination constants for theophylline, 3‐methylxanthine, and 1,3‐ldimethyluric acid. When the methylxanthine content of the methylxanthine‐containing foods and beverages was replaced by caffeine and theophylline in tablet form, kinetics and metabolism of theophylline were the same as in subjects on usual diets.