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. 1985 Feb;19(2):225–232. doi: 10.1111/j.1365-2125.1985.tb02635.x

Comparison of the urinary metabolite profile of caffeine in young and elderly males.

J Blanchard, S J Sawers, J H Jonkman, D D Tang-Liu
PMCID: PMC1463701  PMID: 3986081

Abstract

The urinary metabolite profile of caffeine was compared in a group of seven healthy young men aged 18-29 years and in a group of five healthy elderly men aged 66-71 years. All subjects were given 5 mg/kg doses of caffeine as an aqueous oral solution or an intravenous infusion on two separate occasions in a randomized crossover design. Urine samples were collected for 24 h after dosing and analysed for caffeine and eleven of its metabolites by high-performance liquid chromatography. The effects of age, route of administration, and order of administration by route on the metabolite profile of caffeine were examined. The route of administration and the order of administration by the two routes were found not to influence the urinary metabolite pattern significantly. The urinary metabolite profile did not vary substantially with age except for the observation that significantly greater amounts of 1-methyluric acid, 7-methyluric acid and 1,7-dimethyluric acid were excreted by the elderly subjects.

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Selected References

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  1. Aldridge A., Aranda J. V., Neims A. H. Caffeine metabolism in the newborn. Clin Pharmacol Ther. 1979 Apr;25(4):447–453. doi: 10.1002/cpt1979254447. [DOI] [PubMed] [Google Scholar]
  2. Aldridge A., Neims A. H. Relationship between the clearance of caffeine and its 7-N-demethylation in developing beagle puppies. Biochem Pharmacol. 1980 Jul 1;29(13):1909–1914. doi: 10.1016/0006-2952(80)90102-1. [DOI] [PubMed] [Google Scholar]
  3. Aldridge A., Neims A. H. The effects of phenobarbital and beta-naphthoflavone on the elimination kinetics and metabolite pattern of caffeine in the beagle dog. Drug Metab Dispos. 1979 Nov-Dec;7(6):378–382. [PubMed] [Google Scholar]
  4. Arnaud M. J., Thelin-Doerner A., Ravussin E., Acheson K. J. Study of the demethylation of [1,3,7-Me-13C] caffeine in man using respiratory exchange measurements. Biomed Mass Spectrom. 1980 Nov;7(11-12):521–524. doi: 10.1002/bms.1200071113. [DOI] [PubMed] [Google Scholar]
  5. Bada H. S., Khanna N. N., Somani S. M., Tin A. A. Interconversion of theophylline and caffeine in newborn infants. J Pediatr. 1979 Jun;94(6):993–995. doi: 10.1016/s0022-3476(79)80247-4. [DOI] [PubMed] [Google Scholar]
  6. Birkett D. J., Miners J. O., Attwood J. Secondary metabolism of theophylline biotransformation products in man--route of formation of 1-methyluric acid. Br J Clin Pharmacol. 1983 Jan;15(1):117–119. doi: 10.1111/j.1365-2125.1983.tb01475.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Blanchard J., Mohammadi J. D., Trang J. M. Elimination of a potential interference in assay for plasma caffeine. Clin Chem. 1981 Apr;27(4):637–639. [PubMed] [Google Scholar]
  8. Blanchard J., Sawers S. J. The absolute bioavailability of caffeine in man. Eur J Clin Pharmacol. 1983;24(1):93–98. doi: 10.1007/BF00613933. [DOI] [PubMed] [Google Scholar]
  9. Bonati M., Celardo A., Galletti F., Latini R., Tursi F., Belvedere G. Kinetics of caffeine metabolism in control and 3-methylcholanthrene induced rat liver microsomes. Toxicol Lett. 1984 Apr;21(1):53–58. doi: 10.1016/0378-4274(84)90223-6. [DOI] [PubMed] [Google Scholar]
  10. Bonati M., Latini R., Galletti F., Young J. F., Tognoni G., Garattini S. Caffeine disposition after oral doses. Clin Pharmacol Ther. 1982 Jul;32(1):98–106. doi: 10.1038/clpt.1982.132. [DOI] [PubMed] [Google Scholar]
  11. Boutroy M. J., Vert P., Royer R. J., Monin P., Royer-Morrot M. J. Caffeine, a metabolite of theophylline during the treatment of apnea in the premature infant. J Pediatr. 1979 Jun;94(6):996–998. doi: 10.1016/s0022-3476(79)80248-6. [DOI] [PubMed] [Google Scholar]
  12. Brazier J. L., Descotes J., Lery N., Ollagnier M., Evreux J. C. Inhibition by idrocilamide of the disposition of caffeine. Eur J Clin Pharmacol. 1980 Jan;17(1):37–43. doi: 10.1007/BF00561675. [DOI] [PubMed] [Google Scholar]
  13. Burg A. W., Stein M. E. Urinary excretion of caffeine and its metabolites in the mouse. Biochem Pharmacol. 1972 Apr 1;21(7):909–922. doi: 10.1016/0006-2952(72)90396-6. [DOI] [PubMed] [Google Scholar]
  14. CORNISH H. H., CHRISTMAN A. A. A study of the metabolism of theobromine, theophylline, and caffeine in man. J Biol Chem. 1957 Sep;228(1):315–323. [PubMed] [Google Scholar]
  15. Callahan M. M., Robertson R. S., Arnaud M. J., Branfman A. R., McComish M. F., Yesair D. W. Human metabolism of [1-methyl-14C]- and [2-14C]caffeine after oral administration. Drug Metab Dispos. 1982 Jul-Aug;10(4):417–423. [PubMed] [Google Scholar]
  16. Callahan M. M., Robertson R. S., Branfman A. R., McComish M. F., Yesair D. W. Comparison of caffeine metabolism in three nonsmoking populations after oral administration of radiolabeled caffeine. Drug Metab Dispos. 1983 May-Jun;11(3):211–217. [PubMed] [Google Scholar]
  17. Crooks J., O'Malley K., Stevenson I. H. Pharmacokinetics in the elderly. Clin Pharmacokinet. 1976;1(4):280–296. doi: 10.2165/00003088-197601040-00003. [DOI] [PubMed] [Google Scholar]
  18. Drouillard D. D., Vesell E. S., Dvorchik B. H. Studies on theobromine disposition in normal subjects. Alterations induced by dietary abstention from or exposure to methylxanthines. Clin Pharmacol Ther. 1978 Mar;23(3):296–302. doi: 10.1002/cpt1978233296. [DOI] [PubMed] [Google Scholar]
  19. Grant D. M., Tang B. K., Kalow W. Variability in caffeine metabolism. Clin Pharmacol Ther. 1983 May;33(5):591–602. doi: 10.1038/clpt.1983.80. [DOI] [PubMed] [Google Scholar]
  20. Grygiel J. J., Birkett D. J. Cigarette smoking and theophylline clearance and metabolism. Clin Pharmacol Ther. 1981 Oct;30(4):491–496. doi: 10.1038/clpt.1981.193. [DOI] [PubMed] [Google Scholar]
  21. Grygiel J. J., Birkett D. J. Effect of age on patterns of theophylline metabolism. Clin Pharmacol Ther. 1980 Oct;28(4):456–462. doi: 10.1038/clpt.1980.188. [DOI] [PubMed] [Google Scholar]
  22. Mitoma C., Lombrozo L., LeValley S. E., Dehn F. Nature of the effect of caffeine on the drug-metabolizing enzymes. Arch Biochem Biophys. 1969 Nov;134(2):434–441. doi: 10.1016/0003-9861(69)90303-8. [DOI] [PubMed] [Google Scholar]
  23. Monks T. J., Caldwell J., Smith R. L. Influence of methylxanthine-containing foods on theophylline metabolism and kinetics. Clin Pharmacol Ther. 1979 Oct;26(4):513–524. doi: 10.1002/cpt1979264513. [DOI] [PubMed] [Google Scholar]
  24. Tang-Liu D. D., Riegelman S. An automated HPLC assay for simultaneous quantitation of methylated xanthines and uric acids in urine. J Chromatogr Sci. 1982 Apr;20(4):155–159. doi: 10.1093/chromsci/20.4.155. [DOI] [PubMed] [Google Scholar]
  25. Tang-Liu D. D., Riegelman S. Metabolism of theophylline to caffeine in adults. Res Commun Chem Pathol Pharmacol. 1981 Dec;34(3):371–380. [PubMed] [Google Scholar]
  26. Tang-Liu D. D., Williams R. L., Riegelman S. Disposition of caffeine and its metabolites in man. J Pharmacol Exp Ther. 1983 Jan;224(1):180–185. [PubMed] [Google Scholar]
  27. Tang-Liu D. D., Williams R. L., Riegelman S. Nonlinear theophylline elimination. Clin Pharmacol Ther. 1982 Mar;31(3):358–369. doi: 10.1038/clpt.1982.46. [DOI] [PubMed] [Google Scholar]
  28. Tang B. K., Grant D. M., Kalow W. Isolation and identification of 5-acetylamino-6-formylamino-3-methyluracil as a major metabolite of caffeine in man. Drug Metab Dispos. 1983 May-Jun;11(3):218–220. [PubMed] [Google Scholar]
  29. Tserng K. Y., Takieddine F. N., King K. C. Developmental aspects of theophylline metabolism in premature infants. Clin Pharmacol Ther. 1983 Apr;33(4):522–528. doi: 10.1038/clpt.1983.71. [DOI] [PubMed] [Google Scholar]
  30. Vestal R. E. Drug use in the elderly: a review of problems and special considerations. Drugs. 1978 Oct;16(4):358–382. doi: 10.2165/00003495-197816040-00004. [DOI] [PubMed] [Google Scholar]
  31. Warszawski D., Ben-Zvi Z., Gorodischer R., Arnaud M. J., Bracco I. Urinary metabolites of caffeine in young dogs. Drug Metab Dispos. 1982 Jul-Aug;10(4):424–428. [PubMed] [Google Scholar]
  32. Warszawski D., Ben-Zvi Z., Gorodischer R. Caffeine metabolism in liver slices during postnatal development in the rat. Biochem Pharmacol. 1981 Dec 1;30(23):3145–3150. doi: 10.1016/0006-2952(81)90511-6. [DOI] [PubMed] [Google Scholar]
  33. Wietholtz H., Voegelin M., Arnaud M. J., Bircher J., Preisig R. Assessment of the cytochrome P-448 dependent liver enzyme system by a caffeine breath test. Eur J Clin Pharmacol. 1981;21(1):53–59. doi: 10.1007/BF00609588. [DOI] [PubMed] [Google Scholar]

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