Pharmacokinetic interaction between zolpidem and ciprofloxacin in healthy volunteers

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 (C-max) were 75.73 +/- 28.34 ng/ml (zolpidem alone) and 80.58 +/- 22.40 ng/ml (zolpidem after pre-treatment with ciprofloxacin). The t(max), times taken to reach C-max, were 0.91 +/- 0.42 and 1.44 +/- 0.61 h, respectively, and the total areas under the curve (AUC(0-infinity)) 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 C-max, t(max), AUC(0-infinity), 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.