| Autor: |
Nix, David E., Di Cicco, Robert A., Miller, Ann K., Boyle, Duane A., Boike, Steven C., Zariffa, Nevine, Jorkasky, Diane K., Schentag, Jerome J. |
| Zdroj: |
Journal of Clinical Pharmacology; Aug1999, Vol. 39 Issue 8, p855-865, 11p |
| Abstrakt: |
The potential for nonprescription cimetidine (200 mg twice daily) to affect the pharmacokinetics of sustained-release (SR) 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 mg/ml. To determine individual theophylline dose, a test dose of aminophyl-line 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 theophyl-line 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. [ABSTRACT FROM PUBLISHER] |
| Databáze: |
Complementary Index |
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