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

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: Cmax, tmax, t1/2z, AUC, MRT, and half-value duration (HVD). Comparisons between treatments were performed by ANOVA (α=0.05). Results The initial absorption phase of zolpidem MR formulations was as fast as that of standard zolpidem with no significant difference in tmax. With zolpidem MR 12.5 mg, Cmax 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 tmax and terminal half-life. Clinical Pharmacology & Therapeutics (2005) 77, P44–P44; doi: 10.1016/j.clpt.2004.12.062