ASSESSMENT OF FLUVOXAMINE EFFECTS ON THE
PHARMACOKINETICS OF ZOLPIDEM AND ITS METABOLITE IN
HEALTHY VOLUNTEERS
ANA-MARIA GHELDIU1, ADINA POPA2, MARIA NEAG3, DANA MUNTEAN1, CORINA BOCSAN3, ANCA BUZOIANU3, LAURIAN VLASE1*, MARCELA ACHIM1, IOANA TODOR1, CORINA BRICIU2
1University of Medicine and Pharmacy “Iuliu Hatieganu”, Faculty of Pharmacy, Department of Pharmaceutical Technology
and Biopharmaceutics, Victor Babes 41, RO-400012, Cluj-Napoca, Romania
2University of Medicine and Pharmacy “Iuliu Hatieganu”, Faculty of Pharmacy, Department of Clinical Pharmacy, Ion
Creanga 12, RO-400010, Cluj-Napoca, Romania
3University of Medicine and Pharmacy, "Iuliu Hatieganu”, Faculty of Medicine, Department of Pharmacology, Toxicology
and Clinical Pharmacology, Gheorghe Marinescu 23, RO-400337, Cluj-Napoca, Romania
*corresponding author: vlaselaur@yahoo.com; laurian.vlase@umfcluj.ro
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Abstract:
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 (t½).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.






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