Effect of the Addition of Ciprofloxacin on Theophylline Pharmacokinetics in Subjects Inhibited by Cimetidine

OBJECTIVE:Although the effect of individual enzyme inhibitors on hepatic microsomal enzyme activity has been studied extensively, little data exist on the effects of combinations of inhibiting agents. The purpose of this study was to investigate the effect of the addition of a second hepatic oxidative enzyme inhibitor on the inhibition of metabolism in subjects already maximally inhibited by cimetidine. Ciprofloxacin was used as the second inhibitor.DESIGN:In a randomized crossover sequence, subjects received theophylline 5 mg/kg on day 6 of therapy with cimetidine 2400 mg/d, ciprofloxacin 1 g/d, both drugs, or while drug-free.SETTING:National Institutes of Health-funded General Clinical Research Center.PARTICIPANTS:Eight normal volunteers (6 men, 2 women; mean age 25.2 y).OUTCOME MEASURES:Theophylline pharmacokinetic parameters after each treatment were determined by model independent pharmacokinetic analysis. Statistical analysis of the data for differences between treatments was assessed by ANOVA for r...