Pharmacodyamics and mechanism of action
Eszopiclone is a drug belonging to the group of "Z-drugs". It rapidly induces sleep and shortens the time it takes to fall asleep. It also helps maintain sleep and prevents frequent awakenings. Eszopiclone, unlike other hypnotics, is not a benzodiazepine. It is the active stereoisomer of zopiclone and belongs to the cyclopyrrolone chemical group. Cyclopyrrolones are characterized by high efficacy and low toxicity and are a safer alternative to other drugs for insomnia.
The exact mechanism of action of eszopiclone is not yet known, but it is thought to occur via binding to GABA receptor complexes at binding sites near benzodiazepine receptors, which may explain its hypnotic and sedative effects. It has a particular affinity for GABA-A receptor subunits. GABA-A channels are important inhibitory channels that cause depression in the CNS when their receptors are activated. This may explain the depressant properties of eszopiclone.
Pharmacokinetics
Eszopiclone is rapidly absorbed, with maximum concentration reached within approximately one hour after oral ingestion. Consumption of high-fat foods has been shown to slow absorption. The steady-state concentrations of eszopiclone are reached within 24-48 hours. The drug is 50-60% bound to plasma proteins. After oral administration, eszopiclone is completely biotransformed and the major metabolites are largely inactive. The enzymes involved in the metabolism of eszopiclone are CYP3A, CYP2C8, and CYP2E1. Only about 10% of an eszopiclone dose is excreted as a parent compound in the urine. Up to 75% of an orally administered dose is excreted in the urine as metabolites. The half-life is approximately 6 hours in healthy patients but is prolonged in various patients, including patients with impaired hepatic function, elderly patients, and patients taking CYP3A enzyme inhibitors.
Drug Interactions
There is an increased risk of central nervous system depression when eszopiclone is taken with other drugs that depress the central nervous system, including antipsychotics, sedative hypnotics (such as barbiturates or benzodiazepines), antihistamines, opioids, phenothiazines, and some antidepressants.
There is also an increased risk of central nervous depression with other drugs that inhibit the metabolic activity of the CYP3A4 enzyme system in the liver. Drugs that inhibit this enzyme include nelfinavir, ritonavir, ketoconazole, itraconazole, and clarithromycin.
The effect of alcohol is increased when taken concomitantly with eszopiclone.
