The effect of increased caffeine intake on the metabolism and pharmacokinetics of theophylline in man

The metabolism and pharmacokinetics of intravenously administered theophylline (100 mg) have been investigated in three healthy male volunteers who consumed 6 bottles day of a cola beverage, in addition to their usual intake of methylxanthines, for 7 days prior to and during the study. Five urinary metabolites were detected in addition to unchanged theophylline, that is 3‐methylxanthine, 1.3‐dimethyluric acid, 1‐methyluric acid, and two minor unknown metabolites. The elimination of theophylline, 1.3‐dimethyluric acid, 1‐methyluric acid, and the two unknowns was described by first‐order kinetics, whereas that of 3‐methylxanthine was described by Michaelis‐Menten kinetics. The results have been compared with those previously obtained in the same volunteers while consuming their usual intake of methylxanthine‐containing foods and beverages, and this shows that the addition of extra methylxanthines to the diet does not influence the disposition of theophylline. This is in marked contrast to the effect of deprivation of dietary methylxanthines on theophylline metabolism. The results are discussed in terms of the influence of methylxanthines on theophylline metabolism, and of its possible dose‐ dependency.