TY - JOUR
T1 - Influence of methylxanthine-containing foods on theophylline metabolism and kinetics
AU - Monks, Terrence J.
AU - Caldwell, John
AU - Smith, Robert L.
PY - 1979/10
Y1 - 1979/10
N2 - 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-dimethyluric 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.
AB - 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-dimethyluric 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.
UR - http://www.scopus.com/inward/record.url?scp=0018704730&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0018704730&partnerID=8YFLogxK
U2 - 10.1002/cpt1979264513
DO - 10.1002/cpt1979264513
M3 - Article
C2 - 487699
AN - SCOPUS:0018704730
SN - 0009-9236
VL - 26
SP - 513
EP - 524
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
IS - 4
ER -