Brands, Medical Use, Clinical Data
- Tablet (oral - 5 mg, 10 mg)
Brands / Synonyms
Ambien; Ambien CR; Edluar; Ivadal; Lorex; Niotal; Stilnoct; Stilnox; Zolpidem tartrate; Zolpidemum [Latin]
For the short-term treatment of insomnia.
Zolpidem is a sedative or hypnotic agent with a chemical structure unrelated to benzodiazepines, barbiturates, or other drugs with known hypnotic properties. It interacts with a GABA-BZ receptor complex and shares some of the pharmacological properties of the benzodiazepines. In contrast to the benzodiazepines, which non-selectively bind to and activate all three alpha receptor subtypes, zolpidem in vitro binds the (alpha1) receptor preferentially. The (alpha1) receptor is found primarily on the Lamina IV of the sensorimotor cortical regions, substantia nigra (pars reticulata), cerebellum molecular layer, olfactory bulb, ventral thalamic complex, pons, inferior colliculus, and globus pallidus.
Mechanism of Action
Zolpidem modulates the alpha-subunit, known as the benzodiazepine receptor, within the GABAA receptor chloride channel macromolecular complex. Unlike the benzodiazepines, which non-selectively interact with all three alpha-receptor subtypes, Zolpidem preferentially binds to the alpha-1 receptor.
Zolpidem is rapidly absorbed from the GI tract.
Oral (male rat) LD50 = 695 mg/kg. Symptoms of overdose include impairment of consciousness ranging from somnolence to light coma.
Biotrnasformation / Drug Metabolism
Zolpidem is converted to inactive metabolites in the liver.
Zolpidem tartrate was evaluated in healthy volunteers in single-dose interaction studies for several CNS drugs. A
study involving haloperidol and zolpidem revealed no effect of haloperidol on the pharmacokinetics or
pharmacodynamics of zolpidem. Imipramine in combination with zolpidem produced no pharmacokinetic interaction other a
20% decrease in peak levels of imipramine, but there was an additive effect of decreased alertness. Similarly,
chlorpromazine in combination with zolpidem produced no pharmacokinetic interaction, but there was an additive effect
of decreased alertness and psychomotor performance. The lack of a drug interaction following single-dose
administration does not predict a lack following chronic administration.
An additive effect on psychomotor performance between alcohol and zolpidem was demonstrated.
A single-dose interaction study with zolpidem 10 mg and fluoxetine 20 mg at steady-state levels in male volunteers
did not demonstrate any clinically significant pharmacokinetic or pharmacodynamic interactions. When multiple doses
of zolpidem and fluoxetine at steady-state concentrations were evaluated in healthy females, the only significant
change was a 17% increase in the zolpidem half-life. There was no evidence of an additive effect in psychomotor
Following five consecutive nightly doses of zolpidem 10 mg in the presence of sertraline 50 mg (17 consecutive
daily doses, at 7:00 am, in healthy female volunteers), zolpidem C max was significantly higher (43%) and
T max was significantly decreased (53%). Pharmacokinetics of sertraline and N-desmethylsertraline were
unaffected by zolpidem.
Since the systemic evaluation of zolpidem tartrate in combination with other CNS-active drugs have been limited,
careful consideration should be given to the pharmacology of any CNS-active drug to be used with zolpidem. Any drug
with CNS-depressant effects could potentially enhance the CNS- depressant effects of zolpidem.
Drugs that affect drug metabolism via cytochrome P450: A randomized, double-blind, crossover
interaction study in ten healthy volunteers between itraconazole (200 mg once daily for 4 days) and a single dose of
zolpidem (10 mg) given 5 hours after the last dose of itraconazole resulted in a 34% increase in
AUC0->∞ of zolpidem. There were no significant pharmacodynamic effects of zolpidem on subjective
drowsiness, postural sway, or psychomotor performance.
A randomized, placebo-controlled, crossover interaction study in eight healthy female volunteers between 5
consecutive daily doses of rifampin (600 mg) and a single dose of zolpidem (20 mg) given 17 hours after the last dose
of rifampin showed significant reductions of the AUC (ñ73%), Cmax (ñ58%), and
T1/2 (ñ36%) of zolpidem together with significant reductions in the pharmacodynamic effects of
A study involving cimetidine/zolpidem and ranitidine/zolpidem combinations revealed no effect of either drug on
the pharmacokinetics or pharmacodynamics of zolpidem. Zolpidem had no effect on digoxin kinetics and did not effect
prothrombin time when given with warfarin in normal subjects. Zolpidem's sedative/hypnotic effect was reversed by
flumazenil; however, no significant alterations in zolpidem pharmacokinetics were found.