EEG profile of intravenous zolpidem in healthy volunteers

Zolpidem is an imidazopyridine which binds specifically to the ω₁ receptor. Zolpidem demonstrated potent hypnotic activity at a dose of 10 mg. Pharmacodynamics and pharmacokinetics of zolpidem were studied after daytime administration in a randomised, double-blind, placebo-controlled, cross-over trial. Single doses of zolpidem (10 mg IV as a 3-min infusion and 20 mg orally) and placebo were firstly tested in 12 healthy young male volunteers. Two other doses (5 mg IV and orally) were then evaluated in 6 out of these 12 subjects. EEG (4 leads = Fp2-T4, Fp1-T3, T4-02 and T3-01), and Stanford Sleepiness Scale (SSS) were measured up to 5 h post-dosing. Blood samples were also collected up to 24 h. The time course of the hypnotic activity of zolpidem, assessed by the score obtained on SSS, showed a similar profile whatever the route or the dose administered: slightly earlier onset after IV but sedative scores were reached at 30 min and the effect peaked between 1 and 1.5 h and lasted 4 h in both conditions. The EEG profile of zolpidem was characterised by a decrease of alpha activity and an increase in delta and in beta activity. The effect on beta activity was marked within the first hour and then disappeared. The time course of delta and alpha activities indicated a rapid onset (10 min after IV, 30 min after oral route) and a duration of 3–4 h. The amplitude of these relative EEG changes and their duration were independent of the route of administration and the dose administered. AUC and C_max increased proportionally to the administered dose and elimination half life (2 h), clearance and volume of distribution did not change according to the dose or the route of administration. T_max was 1 h after the oral administration. The absolute bioavailability was about 70%. In conclusion, EEG induced changes and score of SSS were in good correlation with what has been observed with insomniac patients: zolpidem has a rapid onset and a short duration of action.