The Influence of Intravenous Cimetidine Dosage Regimens on the Disposition of Theophylline

Abstract

The influence of the method of cimetidine administration on theophylline disposition was studied in nine healthy, cigarette smoking male volunteers. The treatment phases consisted of: A) theophylline alone, B) theophylline plus intermittent cimetidine therapy (300 mg IV every 6 hr), and C) theophylline in combination with continuous infusion cimetidine (50 mg/hr). Theophylline (4.8 mg/kg) was administered intravenously as aminophylline over 30 minutes during each treatment phase. During study phases B and C subjects received 48 hours of cimetidine therapy beginning 24 hours prior to theophylline dosing. Blood samples for determination of theophylline concentrations were collected serially over 24 hours. Serum theophylline concentrations were determined in duplicate using fluorescence polarization immunoassay (Abbott Diagnostic TDx). The average age of the subjects was 27.4 +/- 4.7 years, and the individual smoking histories ranged from 0.5 to 1.5 packs per day (average 0.89 +/- 0.33). The mean (+/- SD) body weight was 79.1 +/- 8.2 kg and all subjects were within 20% of their ideal body weight. Theophylline pharmacokinetic parameters were determined using noncompartmental analysis. ANOVA for repeated measures and Tukey's multiple comparison test were used for statistical analysis. The mean (+/- SD) theophylline clearance for each of the treatment groups was: 1.4 +/- 0.4, 1.2 +/- 0.3, and 1.2 +/- 0.2 ml/min/kg for phases A, B and C, respectively. Cimetidine decreased the clearance of theophylline, however, theophylline clearance was not statistically different between regimens B and C. Thus, the method of cimetidine administration (intermittent versus continuous infusion) did not influence the magnitude of the drug-drug interaction.