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.
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