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Comparative pharmacokinetics of caffeine in young and elderly men

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Abstract

The phamacokinetic behavior of caffeine was compared in a group of eight healthy young men aged 20.5±2.0 years (mean ± SD), and in a group of eight healthy, elderly men aged 71.2±3.9 years. Each subject was given a 5 mg/kg dose of caffeine as either an aqueous oral solution or an intravenous infusion over 30 min using a randomized crossover design. Plasma and urine samples were collected for 24 hr following each dose and analyzed for caffeine content using high-performance liquid chromatography.

The peak times (tmax), peak concentrations (Cmax), and the percentage of the peroral dose systemically available, F(%), were essentially identical in both age groups, indicating that caffeine was absorbed rapidly and completely after peroral administration. These results also indicated that the first-pass metabolism observed in rats following the peroral administration of caffeine does not occur in either human group studied here. The elimination of caffeine during its terminal disposition phase was log-linear. Several between-group comparisons of other pharmacokinetic parameters were made. Although the average elimination rate constant was greater in the elderly, the difference did not reach statistical significance, possibly because of the considerable intersubject variability in the elimination rate of caffeine, with halflives ranging from 2.27 to 9.87 hr. The average apparent volume of distribution was significantly lower in the elderly subjects while the clearances were slightly, but not significantly, larger in the elderly subjects. It appears that most aspects of the pharmacokinetic behavior of caffeine are very similar in young and elderly men.

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References

  1. J. F. Greden. Coffee, tea and you. The Sciences19:6–11 (1979).

    Article  Google Scholar 

  2. J. M. Ritchie. Central nervous system stimulants, the xanthines. In: L. S. Goodman and A. Gilman (eds.),The Pharmacologic Basis of Therapeutics, fifth ed. Macmillan, New York, 1975, pp. 367–378.

    Google Scholar 

  3. D. A. Holloway. Drug problems in the geriatric patient.Drug Intell. Clin. Pharm. 8:332–342 (1974).

    Google Scholar 

  4. A. D. Bender. Pharmacodynamic principles of drug therapy in the aged.J. Am. Geriatr. Soc. 22:269–303 (1974).

    Article  Google Scholar 

  5. J. W. Gorrod. Absorption, metabolism and excretion of drugs in geriatric subjects.Geront. Clin. 16:30–42 (1974).

    Article  CAS  Google Scholar 

  6. E. J. Triggs and R. L. Nation. Pharmacokinetics in the aged: a review.J. Pharmacokin. Biopharm. 3:387–418 (1975).

    Article  CAS  Google Scholar 

  7. J. Crooks, K. O'Malley, and I. H. Stevenson. Pharmacokinetics in the elderly.Clin. Pharmacokin. 1:280–296 (1976).

    Article  CAS  Google Scholar 

  8. A. Aldridge, J. V. Aranda, and A. H. Neims. Caffeine metabolism in the newborn.Clin. Pharmacol. Ther. 25:447–453 (1979).

    CAS  PubMed  Google Scholar 

  9. J. Axelrod and J. Reichenthal. The fate of caffeine in man and a method for its estimation in biological material.J. Pharmacol. Exp. Ther. 107:519–523 (1953).

    CAS  PubMed  Google Scholar 

  10. H. H. Cornish and A. A. Christman. A study of the metabolism of theobromine, theophylline, and caffeine in man.J. Biol. Chem. 218:315–323 (1957).

    Google Scholar 

  11. W. D. Parsons and A. H. Neims. Effect of smoking on caffeine clearance.Clin. Pharmacol. Ther. 24:40–45 (1978).

    CAS  PubMed  Google Scholar 

  12. J. M. Trang, J. Blanchard, K. A. Conrad, and G. G. Harrison. Effect of vitamin C on the pharmacokinetics of caffeine in elderly men.Am. J. Clin. Nutr. 35:487–494 (1982).

    CAS  PubMed  Google Scholar 

  13. J. Blanchard, J. D. Mohammadi, and K. A. Conrad. Improved liquid-chromatographic determination of caffeine in plasma.Clin. Chem. 26:1351–1354 (1980).

    CAS  PubMed  Google Scholar 

  14. J. Blanchard, J. D. Mohammadi, and J. M. Trang. Elimination of a potential interference in assay for plasma caffeine.clin. Chem. 27:637–639 (1981).

    CAS  PubMed  Google Scholar 

  15. M. Jaffé, Ueber den niederschlag welchen pikrinsaure in normalem harn erzeugt und über eine neue reaction des kreatinins.Hoppe Seylers Z. Physiol. Chem. 10:391–400 (1886).

    Google Scholar 

  16. J. Blanchard, Plasma protein binding of caffeine in young and elderly men.J. Pharm. Sci.,71:1415–1418 (1982).

    Article  CAS  PubMed  Google Scholar 

  17. J. A. Nelder and R. Mead. A simplex method for function minimization.Computer J. 7:308–313 (1965).

    Article  Google Scholar 

  18. J. H. Ottaway. Normalization in the fitting of data by iterative methods.Biochem. J. 134:729–736 (1973).

    CAS  PubMed Central  PubMed  Google Scholar 

  19. H. G. Boxenbaum; S. Riegelman, and R. M. Elashoff. Statistical estimations in pharmacokinetics.J. Pharmacokin. Biopharm. 2:123–148 (1974).

    Article  CAS  Google Scholar 

  20. D. S. Riggs.The Mathematical Approach to Physiological Problems. Williams and Wilkins, Baltimore, 1963, p. 51.

    Google Scholar 

  21. M. Gibaldi and D. Perrier.Pharmacokinetics. Marcel Dekker, New York, 1975.

    Google Scholar 

  22. R. A. Upton, S. Riegelman, and L. B. Sheiner. Bioavailability assessment as influenced by changes in drug disposition. In: K. S. Albert (ed.),Drug Absorption and Disposition: Statistical Considerations. Am. Pharm. Assoc., Washington, D.C., 1980, pp. 77–85.

    Google Scholar 

  23. Anon.Scientific Tables, K. Diem and C. Lentner (eds.), Ciba-Geigy, Basel, 1970, p. 711.

  24. M. Sheehan and P. Haythorn. Rapid gas-chromatographic determination of underivatized theophylline in whole blood.J. Chromatogr. 117:393–398 (1976).

    Article  CAS  Google Scholar 

  25. M. A. Peat and T. A. Jennison. Analysis of theophylline in serum and whole blood samples by high-pressure liquid chromatography.J. Analyt. Toxicol. 1:204–207 (1977).

    Article  CAS  Google Scholar 

  26. J. P. Kampmann and J. E. Molholm Hansen. Renal excretion of drugs. In:Drugs and the Elderly—Perspectives in Geriatric Clinical Pharmacology. University Park Press, Baltimore, 1979, pp. 77–87.

    Google Scholar 

  27. A. Aldridge, W. D. Parsons, and A. H. Neims. Stimulation of caffeine metabolism in the rat by 3-methylcholanthrene.Life Sci. 21:967–974 (1977).

    Article  CAS  PubMed  Google Scholar 

  28. R. Latini, M. Bonati, D. Castelli, and S. Garattini. Dose-dependent kinetics of caffeine in rats.Toxicol. Lett. 2:267–270 (1978).

    Article  CAS  Google Scholar 

  29. S. Garattini. Third international caffeine workshop.Nutr. Rev. 39:183–191 (1981).

    Google Scholar 

  30. R. Latini, M. Bonati, E. Marzi, M. T. Tacconi, B. Sadurska, and A. Bizzi. Caffeine disposition and effects in young and one-year old rats.J. Pharm. Pharmacol. 32:596–599 (1980).

    Article  CAS  PubMed  Google Scholar 

  31. W. D. Parsons, J. V. Aranda, and A. H. Neims. Elimination of transplacentally acquired caffeine in full-term neonates.Pediatr. Res. 10:333 (1976).

    Google Scholar 

  32. J. V. Aranda, W. Gorman, E. W. Outerbridge, and A. H. Neims. Pharmacokinetic disposition of caffeine in premature neonates with apnea.Pediatr. Res. 11:414 (1977).

    Article  Google Scholar 

  33. R. Newton, L. J. Broughton, M. J. Lind, P. J. Morrison, H. J. Rogers, and I. D. Bradbrook. Plasma and salivary pharmacokinetics of caffeine in man.Eur. J. Clin. Phamacol. 21:45–52 (1981).

    Article  CAS  Google Scholar 

  34. M. Essam Fikry and M. H. Aboul-Wafa. Intestinal absorption in the old.Geront. Clin. 7:171–178 (1965).

    Article  Google Scholar 

  35. D. P. Richey and A. D. Bender. Pharmacokinetic consequences of aging.Annu. Rev. Pharmacol. Toxicol. 17:49–65 (1977).

    Article  CAS  PubMed  Google Scholar 

  36. I. S. Edelman and J. Liebman. Anatomy of body water and electrolytes.Am. J. Med. 27:256–277 (1959).

    Article  CAS  PubMed  Google Scholar 

  37. J. V. Aranda, J. L. Brazier, A. T. Louridas, and B. I. Sasyniuk. Methylxanthine metabolism in the newborn infant. In: L. F. Soyka and G. P. Redmond (eds.),Drug Metabolism in the Immature Human. Raven Press, New York, 1981, pp. 183–198.

    Google Scholar 

  38. H. Wietholtz, M. Vogelin, M. J. Arnaud, J. Bircher, and R. Preisig. Assessment of the cytochrome P-448 dependent liver enzyme system by a caffeine breath test.Eur. J. Clin. Pharmacol. 21:53–59 (1981).

    Article  CAS  PubMed  Google Scholar 

  39. M. M. Callahan, R. S. Robertson, M. J. Arnaud, A. R. Branfman, M. F. McComish, and D. W. Yesair. Human metabolism of [l-methyl-14C]-and [2-14C] caffeine after oral administration.Drug Metab. Dispos. 10:417–423 (1982).

    CAS  PubMed  Google Scholar 

  40. U. Klotz and G. R. Wilkinson. Hepatic elimination of drugs in the elderly. In: K. Kitani, (ed.),Liver and Aging. Elsevier/North Holland Biomedical Press, New York, 1978, pp. 367–380.

    Google Scholar 

  41. E. J. Antal, P. A. Kramer, S. A. Mercik, D. J. Chapron, and I. R. Lawson. Theophylline pharmacokinetics in advanced age.Br. J. Clin. Pharmacol. 12:637–645 (1981).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. A. H. Neims. Third international caffeine workshop.Nutr. Rev. 39:183–191 (1981).

    Google Scholar 

  43. G. R. Wilkinson and D. G. Shand. A physiological approach to hepatic drug clearance.Clin. Pharmacol. Ther. 18:377–390 (1975).

    CAS  PubMed  Google Scholar 

  44. D. G. Greenblatt, M. Divol Allen, J. S. Harmatz, and R. I. Shader. Diazepam disposition determinants.Clin. Pharmacol. Ther. 27:301–312 (1980).

    Article  CAS  PubMed  Google Scholar 

  45. J. G. Wagner. Simple model to explain effects of plasma protein binding and tissue binding to calculated volumes of distribution, apparent elimination rate constants and clearances.Eur. J. Clin. Pharmacol. 10:425–432 (1976).

    Article  CAS  PubMed  Google Scholar 

  46. R. E. Schneider, H. Bishop, R. A. Yates, C. P. Quarterman, and M. J. Kendall. Effect of age on plasma propranolol levels.Br. J. Clin. Pharmacol. 10:169–170 (1980).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. D. G. Greenblatt and R. I. Shader. Effects of age and other drugs on benzodiazepine kinetics.Arzn. Forsch. 30:886–890 (1980).

    CAS  Google Scholar 

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Authors and Affiliations

  1. Dept. of Pharmaceutical Sciences, College of Pharmacy, University of Arizona, 85721, Tucson, AZ

    James Blanchard

  2. University Dept. of Therapeutics & Clinical Pharmacology, The Royal Infirmary, EH3 9YW, Edinburgh, Scotland

    Stewart J. A. Sawers

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Blanchard, J., Sawers, S.J.A. Comparative pharmacokinetics of caffeine in young and elderly men. Journal of Pharmacokinetics and Biopharmaceutics 11, 109–126 (1983). https://doi.org/10.1007/BF01061844

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