Zolpidem: a nonbenzodiazepine hypnotic for treatment of insomnia

Abstract

The pharmacology, pharmacokinetics, and clinical efficacy of zolpidem tartrate, a new hypnotic agent, are described. Zolpidem belongs to the imidazopyridine class. It exhibits high-affinity binding at a benzodiazepine-receptor subtype that is located in the cerebellum and cerebral cortex but not in the spinal cord or peripheral tissues. It decreases sleep latency and increases total sleep time and sleep efficiency without affecting sleep architecture. Zolpidem tartrate is absorbed rapidly. Bioavailability is 67% after oral doses of 5-20 mg. Pharmacokinetics show age-related and sex-related variations. The disposition of zolpidem is reduced in hepatically and renally impaired patients. Clinical studies have shown effectiveness of zolpidem in increasing sleep time and decreasing sleep latency. It has demonstrated efficacy equal to that of benzodiazepines without causing rebound insomnia or withdrawal effects. Comparative trials have found zolpidem as effective as flunitrazepam, flurazepam, and triazolam. The optimum dose of zolpidem tartrate is 10 mg at bedtime; 5 mg for elderly patients. Adverse reactions to zolpidem are dose-related and have primarily CNS and gastro-intestinal manifestations. Zolpidem exhibits similar efficacy to the benzodiazepines in the treatment of insomnia. Zolpidem's advantages over benzodiazepines are that it does not lead to tolerance, withdrawal phenomena, or REM rebound; however, for short-term, as-needed use, these advantages are not relevant.