title: 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.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, University of Medicine and Pharmacy Iuliu Haţieganu, Emil Isac 13, 400023, Cluj-Napoca, Romania. vlaselaur@yahoo.com
authors.forename: Laurian
authors.initials: L
authors.lastname: Vlase
authors.forename: Adina
authors.initials: A
authors.lastname: Popa
authors.forename: Maria
authors.initials: M
authors.lastname: Neag
authors.forename: Dana
authors.initials: D
authors.lastname: Muntean
authors.forename: Sorin E
authors.initials: SE
authors.lastname: Leucuţa
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000494:pharmacology*; D019540:Area Under Curve; D001682:Biological Availability; D002939:Ciprofloxacin / Q000494:pharmacology*; D004347:Drug Interactions; D006207:Half-Life; D006801:Humans; D006993:Hypnotics and Sedatives / Q000493:pharmacokinetics*; D008297:Male; D011725:Pyridines / Q000493:pharmacokinetics*; D055815:Young Adult; D000077334:Zolpidem
chemical_list: D000890:Anti-Infective Agents; D006993:Hypnotics and Sedatives; D011725:Pyridines; D002939:Ciprofloxacin; D000077334:Zolpidem