Pharmacokinetic evaluation of eszopiclone: clinical and therapeutic implications

Abstract

Eszopiclone is metabolized mainly by Cytochrome P450-3A (CYP3A) isoforms. The mean half-life in healthy nonelderly individuals (6.1 h) is prolonged in the elderly, in patients with hepatic insufficiency, and by coadministration of CYP3A inhibitors. In clinical trials, eszopiclone consistently improves sleep maintenance relative to placebo, based on measures of shortened wake time after sleep onset, and prolonged total sleep time. However eszopiclone may also produce residual sedation and impairment of driving performance in the initial morning waking hours. A bitter or metallic taste is a common though non-serious adverse effect of eszopiclone. Overall, eszopiclone provides a therapeutic option for patients with sleep maintenance problems, though with accompanying potential for residual morning sedation, as well as a relatively high dollar cost of treatment.

Eszopiclone: Review and Clinical Applications in Chronic and Comorbid Insomnia

“…Hence, virtually all sedative and hypnotic activity of the racemate is attributable to S(+)-zopiclone, while R(À)-zopiclone is not only almost inactive but more toxic than racemic zopiclone. This is consistent with the recommended dosage of eszopiclone being approximately 50 % lower compared to its racemate (Greenblatt and Zammit 2012). It has been proposed that cyclopyrrolones, like eszopiclone, may exhibit more selectivity for certain subunits of the GABA A receptor than benzodiazepines, which could translate to a lower incidence of adverse events including rebound insomnia and withdrawal effects (Monti and Pandi-Perumal 2007).…”

“…Both metabolites appear in plasma exposure at lower levels than the parent drug, suggesting that the clinical activity of eszopiclone is due mainly to the parent drug (Greenblatt and Zammit 2012).…”

Gender differences in pharmacokinetics and pharmacodynamics of zolpidem following sublingual administration

“…In the same studies, there was no meaningful difference between adult men and women in the pharmacodynamic (PD) response to triazolam. The effect of gender on the pharmacokinetics (PK) or PD of eszopiclone has not been reported …”

Stereo‐Psychopharmacology: The Case of Citalopram and Escitalopram

“…Benefits of some enantiopure drugs (eg, eszopiclone) relative to racemic mixtures are uncertain. 10,13,14 Regardless, newly patented enantiopure drugs are likely to have high dollar costs.…”

“…Some enantiopure psychotropic drugs, such as armodafinil and esketamine, may have clinically important pharmacokinetic and/or pharmacodynamic differences from the corresponding racemic mixtures. Benefits of some enantiopure drugs (eg, eszopiclone) relative to racemic mixtures are uncertain . Regardless, newly patented enantiopure drugs are likely to have high dollar costs.…”