Pharmacokinetic evaluation of eszopiclone: clinical and therapeutic implications
Abstract
INTRODUCTION: Eszopiclone is the active S-enantiomer of R,S-zopiclone, and is a cyclopyrrolone hypnotic acting via the GABA-benzodiazepine receptor system. Nearly 6 million prescriptions for eszopiclone are written yearly in the United States. AREAS COVERED: This paper addresses the pharmacokinetic properties of eszopiclone and the extent to which the longer half-life of eszopiclone compared to other commonly used hypnotics (immediate-release zolpidem, modified-release zolpidem, triazolam, zaleplon) may translate into either improved efficacy in enhancing sleep maintenance, or increased probability of residual sedative or performance-impairing effects. EXPERT OPINION: 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.
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Current evidence does not support the development of tolerance or rebound insomnia following eszopiclone discontinuation in primary insomnia patients.
“Nevertheless, current evidence 33 34 35 36 37 does not support the development of tolerance or rebound insomnia following eszopiclone discontinuation in primary insomnia patients.”
From Z-drug abuse and dependence: Clinical guideline of the Brazilian Academy of Neurology for diagnosis and management (2025) · cites this paper as [33]
The sublingual formulation of zolpidem achieves earlier and higher peak plasma levels than the immediate-release oral form, even at lower doses, a pharmacokinetic profile that may contribute to its greater abuse potential.
“Notably, the sublingual formulation achieves earlier and higher peak plasma levels than the immediate-release oral form, even at lower doses—a pharmacokinetic profile that may contribute to its greater abuse potential.”
From Z-drug abuse and dependence: Clinical guideline of the Brazilian Academy of Neurology for diagnosis and management (2025) · cites this paper as [33]
Immediate-release and sublingual formulations of zolpidem are characterized by rapid absorption and higher initial plasma concentrations, factors that likely enhance the risk of behavioral reinforcement and recreational use.
“Immediate-release and sublingual formulations of zolpidem are characterized by rapid absorption and higher initial plasma concentrations, factors that likely enhance the risk of behavioral reinforcement and recreational use.”
From Z-drug abuse and dependence: Clinical guideline of the Brazilian Academy of Neurology for diagnosis and management (2025) · cites this paper as [33]
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- Authors
- Greenblatt, D. J., & Zammit, G. K.
- Affiliations
- Tufts University (US)
- Clinilabs (United States) (US)
- Venue
- Expert Opinion on Drug Metabolism & Toxicology
- Publisher
- Informa UK Limited
- Published
- 2012-11-06
- Volume
- 8
- Issue
- 12
- Pages
- 1609-1618
- ISSN
- 1742-5255 (ISSN-L)
- 1744-7607
- OpenAlex
- W2144746408
- Cited by
- 28
- References
- 86
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 1 · 2013: 3
- FWCI
- 2.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Expert Opinion on Drug Metabolism & Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
- Keywords
- eszopiclone, pharmacokinetics, GABA-benzodiazepine receptor complex, CYP3A metabolism, drug interactions, sleep maintenance, residual sedation, taste disorders, elderly patients, liver dysfunction, zolpidem, triazolam, zaleplon
- MeSH terms
- Eszopiclone, Zolpidem, Acetamides, Adult, Aged, Clinical Trials as Topic, Drug Interactions, Half-Life, Humans, Hypnotics and Sedatives, Sleep Initiation and Maintenance Disorders, Piperazines, Pyridines, Pyrimidines, Receptors, GABA-A, Sleep, Triazolam, United States, Hepatic Insufficiency, Cytochrome P-450 CYP3A, Azabicyclo Compounds, Cytochrome P-450 CYP3A Inhibitors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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