Zodenox Mechanism of Action

Pharmacology: Pharmacodynamics: Zolpidem tartrate is an imidazopyridine which preferentially binds the omega-1 receptor subtype (also known as the benzodiazepine-1 subtype) which corresponds to GABA-A receptors containing the alpha-1 sub-unit, whereas benzodiazepines non-selectively bind both omega-1 and omega-2 subtypes. The modulation of the chloride anion channel via this receptor leads to the specific sedative effects demonstrated by zolpidem tartrate. These effects are reversed by the benzodiazepine antagonist flumazenil.
Zolpidem tartrate decreases sleep latency and the number of awakenings, and increases sleep duration and sleep quality. These effects are associated with a characteristic EEG profile, different from that of the benzodiazepines. In studies that measured the percentage of time spent in each sleep stage, zolpidem tartrate has generally been shown to preserve sleep stages. At the recommended dose, zolpidem tartrate has no influence on the paradoxical sleep duration (REM). The preservation of deep sleep (stages 3 and 4-slow-wave sleep) may be explained by the selective omega-1 binding by zolpidem tartrate. All identified effects of zolpidem tartrate are reversed by the benzodiazepine antagonist flumazenil.
Pharmacokinetics: Zolpidem tartrate has both a rapid absorption and onset of hypnotic action. Bioavailability is 70% following oral administration and demonstrates linear kinetics in the therapeutic dose range. Peak plasma concentration is reached at between 0.5 and 3 hours.
The elimination half-life is short, with a mean of 2.4 hours (± 0.2 h) and a duration of action of up to 6 hours.
Protein binding amounts to 92.5% ± 0.1%. First pass metabolism by the liver amounts to approximately 35%. Repeated administration has been shown not to modify protein binding indicating a lack of competition between zolpidem tartrate and its metabolites for binding sites.
The distribution volume in adults is 0.54 ± 0.02 L/kg and decreases to 0.34 ± 0.05 L/kg in the very elderly.
All metabolites are pharmacologically inactive and are eliminated in the urine (56%) and in the faeces (37%).
Zolpidem tartrate has been shown in trials to be non-dialysable.
Plasma concentrations in elderly subjects and those with hepatic impairment are increased. In patients with renal insufficiency, whether dialysed or not, there is a moderate reduction in clearance. The other pharmacokinetic parameters are unaffected.
Zolpidem tartrate is metabolised via several hepatic cytochrome P450 enzymes, the main enzyme being CYP3A4 with the contribution of CYP1A2. Since CYP3A4 plays an important role in zolpidem tartrate metabolism, possible interactions with drugs that are substrates or inducers of CYP3A4 should be considered.