HUMAN METABOLISM OF [1-METHYL-C-14]- AND [2-C-14]-LABELED CAFFEINE AFTER ORAL-ADMINISTRATION

  • 1 January 1982
    • journal article
    • research article
    • Vol. 10  (4) , 417-423
Abstract
Radiolabeled caffeine was administered orally at 5 mg/kg to adult, male volunteers. Blood, saliva, expired CO2, urine and feces were collected and analyzed for total radiolabeled equivalents, caffeine and its metabolites. High-performance liquid chromatography (HPLC) was the principal technique used to separate caffeine and the various metabolites with quantitation by liquid-scintillation counting. The half-life of caffeine in both serum and saliva was .apprx. 3 h, with the concentration of caffeine in the saliva samples ranging from 65-85% of that found in the serum samples. The major metabolites found in serum and saliva were the dimethylxanthines. In the course of separating the urinary metabolites, the HPLC system partially resolved 2 unidentified polar metabolites arising from radiolabeled caffeine. The major component corresponded to 5-acetylamino-6-amino-3-methyluracil and in the subjects ranged from 7-35% of the administered dose. The other principal urinary metabolites were 1-methylxanthine at .apprx. 18% of the administered dose and 1-methyluric acid at 15%. The fecal samples contained .apprx. 5% of the dose, mainly as uric acid compounds which retained the 1-methyl group. Of the administered radiolabeled dose .apprx. 90% was accounted for and > 95% of the urinary radioactivity was identified as specific metabolites.