Summary
The influence of usual multiple ingestions of dietary caffeine on oral single-dose pharmacokinetics of theophylline has been investigated in 6 healthy male subjects. The subjects consumed 2 to 7 cups of regular instant coffee during the 24 h study period.
Their mean serum concentrations of caffeine varied from 1.2 to 3.1 mg/l. After their usual intake of dietary caffeine, the serum concentrations of theophylline from 3 to 24 h after administration were significantly higher than after deprivation of dietary caffeine. The apparent elimination of theophylline half-life was prolonged from 6.3 (0.61) h (mean with (SEM)) to 8.3 (0.47) h (32% increase, P<0.01) and the total body clearance was reduced from 55.0 (1.31) ml·h−1·kg−1 to 42.5 (2.63) ml·h−1·kg−1 (23% decrase, P<0.001). Saturation of theophylline metabolism and/or competition between theophylline and caffeine metabolism in addition to theophylline derived from caffeine may be the cause of the delayed elimination of theophylline.
The present study has indicated that a significant reduction in theophylline metabolism may be caused by a conventional intake of dietary caffeine. In bronchodilator therapy with theophylline, therefore, the daily consumption of caffeine should be taken into consideration.
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References
Bierman CW, Williams PV (1989) Therapeutic monitoring of theophylline, Rationale and current status. Clin Pharmacokinet 17: 377–384
Grygiel JJ, Wing LMH, Farkas J, Birkett DJ (1979) Effects of allopurinol on theophylline metabolism and clearance. Clin Pharmacol Ther 26: 660–667
Birkett DJ, Dahlqvist R, Miners JO, Lelo A, Billing B (1985) Comparison of theophylline and theobromine metabolism in man. Drug Metab Dispos 13: 725–728
Cornish HH, Christman AA (1957) A study of the metabolism of theobromine, theophylline, and caffeine in man. J Biol Chem 228: 315–323
Jenne JW, Nagasawa HT, Thompson RD (1976) Relationship of urinary metabolites of theophylline to serum theophylline levels. Clin Pharmacol Ther 19: 375–381
Tang-Liu DDS, Williams RL, Riegelman S (1982) Nonlinear theophylline elimination. Clin Pharmacol Ther 31: 358–369
Monks TJ, Caldwell J, Smith RL (1979) Influence of methylxanthine-containing foods on theophylline metabolism and kinetics. Clin Pharmacol Ther 26: 513–524
Monks TJ, Lawrie CA, Caldwell J (1981) The effect of increased caffeine intake on the metabolism and pharmacokinetics of theophylline in man. Biopharm Drug Dispos 2: 31–37
Zilly W, Ziegler M, Richter E (1986) Interaktion zwischen Coffein und Theophyllin. Med Klin 81: 560–562
Jonkman JHG, Sollie FAE, Sauter R, Steinijans VW (1991) The influence of caffeine on the steady-state pharmacokinetics of theophylline. Clin Pharmacol Ther 49: 248–255
Horai Y, Ishizaki T, Sasaki T, Chiba K, Suganuma T, Echizen H, Ohnishi A (1983) Bioavailability and pharmacokinetics of theophylline in plain uncoated and sustained-release dosage forms in relation to smoking habit I. Single dose study. Eur J Clin Pharmacol 24: 79–87
Lelo A, Miners JO, Robson R, Birkett DJ (1986) Assessment of caffeine exposure: Caffeine content of beverages, caffeine intake, and plasma concentrations of methylxanthines. Clin Pharmacol Ther 39: 54–59
James JE, Crosbie J (1987) Somatic and psychological health implications of heavy caffeine use. Br J Addict 82: 503–509
Stavric B, Klassen R, Watkinson B, Karpinski K, Stapley R, Fried P (1988) Variability in caffeine consumption from coffee and tea: Possible significance for epidemiological studies. Food Chem Toxicol 26: 111–118
Bonati M, Latini R, Galletti F, Young JF, Tognoni G, Garattini S (1982) Caffeine disposition after oral doses. Clin Pharmacol Ther 32: 98–106
Tang-Liu DDS, Williams RL, Riegelman S (1983) Disposition of caffeine and its metabolites in man. J Pharmacol Exp Ther 224: 180–185
Grant DM, Tang BK, Kalow W (1983) Variability in caffeine metabolism. Clin Pharmacol Ther 33: 591–602
Weinberger M, Ginchansky E (1977) Dose-dependent kinetics of theophylline disposition in asthmatic children. J Pediatr 91: 820–824
Sarrazin E, Hendeles L, Weinberger M, Muir K, Riegelman S (1980) Dose-dependent kinetics for theophylline: Observations among ambulatory asthmatic children. J Pediatr 97: 825–828
Gundert-Remy U, Hildebrandt R, Hengen N, Weber E (1983) Non-linear elimination processes of theophylline. Eur J Clin Pharmacol 24: 71–78
Ishizaki T, Kubo M (1987) Incidence of apparent Michaelis-Menten kinetic behavior of theophylline and its parameter (Vmax and Km) among asthmatic children and adults. Ther Drug Monit 9: 11–20
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Sato, J., Nakata, H., Owada, E. et al. Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects. Eur J Clin Pharmacol 44, 295–298 (1993). https://doi.org/10.1007/BF00271376
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DOI: https://doi.org/10.1007/BF00271376