The objective of this study was to investigate the effects of fluvoxamine on the pharmacokinetics of zolpidem and its main metabolite, zolpidem phenyl-4-carboxylic acid (Z4CA) in healthy volunteers. The study consisted of 2 periods: Period 1 (Reference), when the volunteers received a single dose of 5 mg zolpidem and Period 2 (Test), when a combination of 5 mg zolpidem and 100 mg fluvoxamine was administered, after a pre-treatment regimen with fluvoxamine for 6 days. The pharmacokinetic parameters of zolpidem and its metabolite were determined by using non-compartmental methods. Pretreatment with fluvoxamine increased the mean peak plasma concentration (Cmax) of zolpidem. Also, after concomitant intake of fluvoxamine, the total area under the curve (AUC0-∞) was significantly increased from 340.34 ± 249.02 to 725.05 ± 429.23 ng*h/mL. As for Z4CA, Cmax was reduced from 117.08 ± 37.55 to 82.33 ± 25.71 ng/mL. After fluvoxamine intake, the clearance of Z4CA was to some extent impaired as suggested by reducing the elimination rate constant (kel) and by prolonging its half-life (t1/2).This study demonstrated that fluvoxamine was responsible for a 2.13-fold exposure to zolpidem and influenced Z4CA pharmacokinetics to a lesser degree. The clinical implications of this interaction need additional studies. © 2015 Romanian Society for Pharmaceutical Sciences. All Right reserved.