¹Sanofi-Synthelabo Research, LARIME, Chilly-Mazarin, France

Abstract

Aims/Background: To evaluate relative bioavailability and plasma pharmacokinetic (PK) profile of single oral doses of zolpidem modified-release (MR) formulations (10 mg and 12.5 mg) compared to standard zolpidem 10 mg.

Methods: 24 healthy, Caucasian, male volunteers (18–45 years old) received single oral doses of zolpidem MR 10 mg and 12.5 mg, or standard zolpidem 10 mg via a randomized, open-label, crossover study. Blood sample (n=18) were collected up to 16h postdose. PK parameters were determined by noncompartmental analysis: C_max, t_max, t_1/2z, AUC, MRT, and half-value duration (HVD). Comparisons between treatments were performed by ANOVA (=0.05).

Results: The initial absorption phase of zolpidem MR formulations was as fast as that of standard zolpidem with no significant difference in t_max. With zolpidem MR 12.5 mg, C_max values were moderately lower (ratio of 0.82) compared with standard zolpidem and plasma concentrations were maintained above those observed with standard zolpidem for a longer period of time, and particularly from 3 to 6h postdose. This was confirmed by an increase of the HVD from 2.3h for standard zolpidem to 4.6h for zolpidem MR 12.5 mg. The mean terminal half-life was similar with all 3 formulations.

Conclusion: These results show that this new zolpidem MR formulation provides the appropriate PK characteristics to extend plasma concentration into the middle of the night (3–6 h postdose), while retaining the same t_max and terminal half-life.