Titre du document / Document title

Pharmacokinetic profile of a new modified release formulation of zolpidem designed to improve sleep maintenance

Auteur(s) / Author(s)

WEINLING Estelle ⁽¹⁾ ; MCDOUGALL Stuart ⁽²⁾ ; ANDRE Frédéric ⁽¹⁾ ; BIANCHETTI Gabrio ⁽¹⁾ ; DUBRUC Catherine ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Sanofi-Synthelabo Research (Sanofi-Aventis group), 91380 Chilly-Mazarin, FRANCE
⁽²⁾ Sanofi-Synthelabo Research (Sanofi-Aventis group), Alnwick, ROYAUME-UNI

Résumé / Abstract

The aim of this study was to compare the relative bioavailability and the pharmacokinetic profile of a single oral dose of a zolpidem modified-release (MR) 12.5-mg formulation with those of the standard 10-mg zolpidem immediate-release (IR) formulation. Absolute bioavailabilities of oral formulations were evaluated using intravenously (i.v.) administered zolpidem as a reference. Twenty-four healthy, Caucasian, male volunteers (18-45 years old) received single doses of three oral formulations (zolpidem-MR 12.5 mg, zolpidem-IR 10 mg and an experimental form) and zolpidem i.v. infusion (8 mg) in a randomized, open-label, crossover trial. Blood samples (18 time-points) were collected up to 16 h post-dose after oral administration and up to 12 h post-dose after i.v. administration. Pharmacokinetic parameters were determined by non-compartmental analysis, allowing comparisons between treatments based on estimated ratios and differences, with 90% confidence intervals. The initial absorption phase of the zolpidem-MR formulation was as fast as that of zolpidem-IR with no significant difference in t_max. With zolpidem-MR 12.5 mg, C_max was moderately lower than with zolpidem-IR (ratio of 0.82), and plasma zolpidem concentrations were maintained above those observed with zolpidem-IR for a longer period of time, particularly from 3 to 6 h post-dose. This was confirmed by an increase in half-value duration (HVD) from 2.3 h with zolpidem-IR to 4.6 h with zolpidem-MR 12.5 mg. The mean terminal half-life was similar between formulations. Zolpidem-MR 12.5 mg provides the appropriate pharmacokinetic characteristics to extend plasma zolpidem concentrations into the middle of the night (3-6 h post-dose), while retaining the same t_max and terminal half-life.

Revue / Journal Title

Fundamental & clinical pharmacology   ISSN 0767-3981   CODEN FCPHEZ 

Source / Source

2006, vol. 20, n^o4, pp. 397-403 [7 page(s) (article)] (15 ref.)

Langue / Language

Anglais

Editeur / Publisher

Blackwell, Oxford, ROYAUME-UNI  (1987) (Revue)

Mots-clés anglais / English Keywords

Sleep wake cycle ; Gabaergic agonist ; Gabaergic receptor A ; Benzodiazepine receptor ; Agonist ; Dosage form ; Sedative ; Hypnotic ; Bioavailability ; Sleep ; Design ; Zolpidem ; Formulation ; Controlled release form ; Pharmacokinetics ;

Mots-clés français / French Keywords

Imidazopyridine dérivé ; Cycle veille sommeil ; Stimulant gabaergique ; Récepteur gabaergique A ; Récepteur benzodiazépinique ; Agoniste ; Forme pharmaceutique ; Sédatif ; Hypnotique ; Biodisponibilité ; Sommeil ; Conception ; Zolpidem ; Formulation ; Forme libération contrôlée ; Pharmacocinétique ;

Mots-clés espagnols / Spanish Keywords

Ciclo sueño vigilia ; Estimulante gabaérgico ; Receptor gabaminérgico A ; Receptor benzodiazepínico ; Agonista ; Forma farmacéutica ; Sedante ; Hipnótico ; Biodisponibilidad ; Sueño ; Diseño ; Zolpidem ; Formulación ; Forma liberación controlada ; Farmacocinética ;

Mots-clés d'auteur / Author Keywords

bioavailability ; modified release ; pharmacokinetics ; zolpidem ;

Localisation / Location

INIST-CNRS, Cote INIST : 14711, 35400013882205.0090