Theobromine kinetics and metabolic disposition.

Metabolism and kinetics of a single oral dose of 30 microCi 8-14C-theobromine with 10 mg/kg theobromine sodium acetate were studied in six healthy, nonmedicated, nonsmoking men after 14 days' abstention from all methylxanthine sources. Identification and quantitation of metabolites in plasma and urine both by HPLC and by thin-layer chromatography coupled with radiography indicated that theobromine was predominant in plasma. For urine, both methods identified theobromine as well as 7-methylxanthine, 7-methyluric acid, 3-methylxanthine, 6-amino-5[N-methylformylamino]-1-methyluracil, and a small amount of 3,7-dimethyluric acid as the metabolites of theobromine. All administered radioactivity was recovered in urine and no polar metabolites could be detected. Analysis of the urinary excretion data by the sigma-minus method allowed calculation of the apparent first-order rate constants for production of 7-methylxanthine, 7-methyluric acid, 3-methylxanthine, 3,7-dimethyluric acid, and 6-amino-5[N-methylformylamino]-1-methyluracil.