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. 1986 Aug;22(2):177–182. doi: 10.1111/j.1365-2125.1986.tb05246.x

Comparative pharmacokinetics of caffeine and its primary demethylated metabolites paraxanthine, theobromine and theophylline in man.

A Lelo, D J Birkett, R A Robson, J O Miners
PMCID: PMC1401099  PMID: 3756065

Abstract

The pharmacokinetics of caffeine (CA), paraxanthine (PX), theobromine (TB) and theophylline (TP) were studied in six healthy male volunteers after oral administration of each compound on separate occasions. The total plasma clearances of CA and PX were similar in value (2.07 and 2.20 ml min-1 kg-1, respectively) as were those for TP and TB (0.93 and 1.20 ml min-1 kg-1, respectively). The unbound plasma clearances of CA and PX were also similar in magnitude (3.11 and 4.14 ml min-1 kg-1, respectively) as were those of TP and TB (1.61 and 1.39 ml min-1 kg-1, respectively). The half-lives of TP and TB (6.2 and 7.2 h, respectively) were significantly longer than those of CA and PX (4.1 and 3.1 h, respectively). The volume of distribution at steady state of TP (0.44 l kg-1) was lower than that of the other methylxanthines (0.63-0.72 l kg-1). The unbound volume of distribution of TP (0.77 l kg-1) was however the same as that of TB (0.79 l kg-1) whereas the unbound volume of distribution of PX (1.18 l kg-1) was similar to that of CA (1.06 l kg-1).

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Selected References

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  1. Benet L. Z., Galeazzi R. L. Noncompartmental determination of the steady-state volume of distribution. J Pharm Sci. 1979 Aug;68(8):1071–1074. doi: 10.1002/jps.2600680845. [DOI] [PubMed] [Google Scholar]
  2. Birkett D. J., Dahlqvist R., Miners J. O., Lelo A., Billing B. Comparison of theophylline and theobromine metabolism in man. Drug Metab Dispos. 1985 Nov-Dec;13(6):725–728. [PubMed] [Google Scholar]
  3. Blanchard J., Sawers S. J. Comparative pharmacokinetics of caffeine in young and elderly men. J Pharmacokinet Biopharm. 1983 Apr;11(2):109–126. doi: 10.1007/BF01061844. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. 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]
  6. Bortolotti A., Jiritano L., Bonati M. Pharmacokinetics of paraxanthine, one of the primary metabolites of caffeine, in the rat. Drug Metab Dispos. 1985 Mar-Apr;13(2):227–231. [PubMed] [Google Scholar]
  7. 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]
  8. 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]
  9. 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]
  10. Houston J. B. Drug metabolite kinetics. Pharmacol Ther. 1981;15(3):521–552. doi: 10.1016/0163-7258(81)90056-5. [DOI] [PubMed] [Google Scholar]
  11. Lelo A., Miners J. O., Robson R., Birkett D. J. Assessment of caffeine exposure: caffeine content of beverages, caffeine intake, and plasma concentrations of methylxanthines. Clin Pharmacol Ther. 1986 Jan;39(1):54–59. doi: 10.1038/clpt.1986.10. [DOI] [PubMed] [Google Scholar]
  12. Miners J. O., Attwood J., Birkett D. J. Theobromine metabolism in man. Drug Metab Dispos. 1982 Nov-Dec;10(6):672–675. [PubMed] [Google Scholar]
  13. Miners J. O., Attwood J., Wing L. M., Birkett D. J. Influence of cimetidine, sulfinpyrazone, and cigarette smoking on theobromine metabolism in man. Drug Metab Dispos. 1985 Sep-Oct;13(5):598–601. [PubMed] [Google Scholar]
  14. Ogilvie R. I. Clinical pharmacokinetics of theophylline. Clin Pharmacokinet. 1978 Jul-Aug;3(4):267–293. doi: 10.2165/00003088-197803040-00002. [DOI] [PubMed] [Google Scholar]
  15. Renner E., Wietholtz H., Huguenin P., Arnaud M. J., Preisig R. Caffeine: a model compound for measuring liver function. Hepatology. 1984 Jan-Feb;4(1):38–46. doi: 10.1002/hep.1840040107. [DOI] [PubMed] [Google Scholar]
  16. Shively C. A., Tarka S. M., Jr, Arnaud M. J., Dvorchik B. H., Passananti G. T., Vesell E. S. High levels of methylxanthines in chocolate do not alter theobromine disposition. Clin Pharmacol Ther. 1985 Apr;37(4):415–424. doi: 10.1038/clpt.1985.65. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Tarka S. M., Jr, Arnaud M. J., Dvorchik B. H., Vesell E. S. Theobromine kinetics and metabolic disposition. Clin Pharmacol Ther. 1983 Oct;34(4):546–555. doi: 10.1038/clpt.1983.212. [DOI] [PubMed] [Google Scholar]

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