Pharmacokinetic interaction between zolpidem and ciprofloxacin in healthy volunteers

Abstract

Our objective was to evaluate a possible pharmacokinetic interaction between zolpidem and ciprofloxacin in healthy volunteers. The study consisted of two periods: Period 1 (reference), when each volunteer received a single dose of 5 mg zolpidem and Period 2 (test), when each volunteer received a single dose of 5 mg zolpidem and 500 mg ciprofloxacin. Between the two periods, the subjects were treated for 5 days with a single daily dose of 500 mg ciprofloxacin. Plasma concentrations of zolpidem were determined during a 12-hour period following drug administration. Pharmacokinetic parameters of zolpidem administered in each treatment period were calculated using non-compartmental analysis and the data from two periods were compared to determine statistically significant differences. In the two periods of treatments, the mean peak plasma concentrations (Cmax) were 75.73±28.34 ng/ml (zolpidem alone) and 80.58±22.40 ng/ml (zolpidem after pre-treatment with ciprofloxacin). The tmax, times taken to reach Cmax, were 0.91±0.42 and 1.44±0.61 h, respectively, and the total areas under the curve (AUC0-∞) were 300.2±115.5 and 438.1±142.6 ng h/ml, respectively. The half-life of zolpidem was 2.39±0.53 h when administered alone and 3.34±0.87 h after pre-treatment with ciprofloxacin. These differences were statistically significant for Cmax, tmax, AUC0-∞, half-life and mean residence time. Ciprofloxacin interacts with zolpidem in healthy volunteers, raising its bioavailability by about 46%. This magnitude of effect is likely to be clinically significant.