The effect of low-dose cimetidine (200 mg twice daily) on the pharmacokinetics of theophylline

D. E. Nix, R. A. Di Cicco, A. K. Miller, D. A. Boyle, S. C. Boike, N. Zariffa, D. K. Jorkasky, J. J. Schentag

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5 Scopus citations


The potential for nonprescription cimetidine (200 mg twice daily) to affect the pharmacokinetics of sustained-release (SB) theophylline was assessed in 26 male subjects, 13 smokers and 13 nonsmokers. This was a concentration-controlled drug interaction study in which the subjects were administered a dose of SR theophylline every 12 hours to provide a mean steady-state concentration between 8 and 15 μg/ml. To determine individual theophylline dose, a test dose of aminophylline was administered, and baseline theophylline pharmacokinetics were determined. Subjects remained on SR theophylline for 23 days and were treated in the following sequence: run-in phase (4 days), treatment 1 (7 days), washout (5 days), and treatment 2 (7 days). During the treatment phases, subjects received cimetidine (200 mg at approximately 08:00 and 12:00) or placebo for 7 days in a randomized crossover fashion. Theophylline pharmacokinetics were determined on days 1, 4, and 7 of both treatment phases. A large day-to-day variability in the oral clearance of theophylline was evident for the theophylline-placebo treatment and the theophylline-cimetidine treatment. Nonprescription strength cimetidine resulted in a mean 5% decrease in theophylline oral clearance on day 1 and a mean 12% decrease on days 4 and 7 combined. There were no significant differences in the cimetidine-theophylline interaction between smokers and nonsmokers. Oral clearance during the nighttime dosing interval was 13% greater than the daytime oral clearance for nonsmokers and 22% greater for smokers, showing a greater circadian rhythm for smokers. In summary, nonprescription doses of cimetidine (400 mg/day) have the potential to produce small changes in theoophylline concentrations during steady-state dosing with SR theophylline; however, this effect appears less than changes that occur as a consequence of theophylline's intrasubject variability. (C) 1999 the American College of Clinical Pharmacology.

Original languageEnglish (US)
Pages (from-to)855-865
Number of pages11
JournalJournal of clinical pharmacology
Issue number8
StatePublished - 1999

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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