title: Effect of fluvoxamine on the pharmokinetics of zolpidem: a two-treatment period study in healthy volunteers.
abstract: 1. Our objective was to evaluate a possible pharmacokinetic interaction between zolpidem and fluvoxamine in healthy volunteers. 2. 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 100 mg fluvoxamine. Between the two periods, the subjects were treated for 6 days with a single daily dose of 100 mg fluvoxamine. 3. Pharmacokinetic parameters of zolpidem given in each treatment period were calculated using non-compartmental analysis and the data from two periods were compared to determine statistically significant differences. 4. In the two periods of treatments, the mean peak plasma concentrations (C(max)) were 56.4 ± 25.6 ng/mL (zolpidem alone) and 67.3 ± 25.8 ng/mL (zolpidem after pretreatment with fluvoxamine). The t(max), times taken to reach C(max), were 0.83 ± 0.44 and 1.26 ± 0.74 h, respectively, and the total areas under the curve (AUC(0-∞)) were 200.9 ± 116.8 and 512.0 ± 354.6 ng h/mL, respectively. The half-life of zolpidem was 2.24 ± 0.81 h when given alone and 4.99 ± 2.92 h after pretreatment with fluvoxamine. 5. Fluvoxamine interacts with zolpidem in healthy volunteers and increases its exposure by approximately 150%. The experimental data showed the pharmacokinetic interaction between zolpidem and fluvoxamine, and suggest that the observed interaction might be clinically significant, but its relevance has to be confirmed.
authors: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, University of Medicine and Pharmacy Iuliu Haţieganu, Cluj-Napoca, Romania. vlaselaur@yahoo.com
authors: Laurian
authors: L
authors: Vlase
authors: Adina
authors: A
authors: Popa
authors: Maria
authors: M
authors: Neag
authors: Dana
authors: D
authors: Muntean
authors: Marcela
authors: M
authors: Achim
authors: Sorin Emilian
authors: SE
authors: Leucuţa
mesh_terms: D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000494:pharmacology*; D001682:Biological Availability; D018592:Cross-Over Studies; D004347:Drug Interactions; D016666:Fluvoxamine / Q000009:adverse effects / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D011725:Pyridines / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D055815:Young Adult; D000077334:Zolpidem
chemical_list: D018687:Antidepressive Agents, Second-Generation; D016666:Fluvoxamine; D058785:GABA-A Receptor Agonists; D006993:Hypnotics and Sedatives; D011725:Pyridines; D017367:Selective Serotonin Reuptake Inhibitors; D000077334:Zolpidem