title: Pharmacokinetic evaluation of eszopiclone: clinical and therapeutic implications.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Tufts University School of Medicine, Tufts Medical Center, Department of Molecular Physiology and Pharmacology, Sackler Program in Pharmacology and Experimental Therapeutics, 136 Harrison Avenue, Boston, MA 02111, USA. dj.greenblatt@tufts.edu
authors.forename: David J
authors.initials: DJ
authors.lastname: Greenblatt
authors.forename: Gary K
authors.initials: GK
authors.lastname: Zammit
mesh_terms: D000081:Acetamides / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D053961:Azabicyclo Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D051544:Cytochrome P-450 CYP3A / Q000494:pharmacology; D065692:Cytochrome P-450 CYP3A Inhibitors; D004347:Drug Interactions; D000069582:Eszopiclone; D006207:Half-Life; D048550:Hepatic Insufficiency / Q000150:complications / Q000188:drug therapy; D006801:Humans; D006993:Hypnotics and Sedatives / Q000627:therapeutic use; D010879:Piperazines / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D012890:Sleep / Q000187:drug effects; D007319:Sleep Initiation and Maintenance Disorders / Q000150:complications / Q000188:drug therapy; D014229:Triazolam / Q000627:therapeutic use; D014481:United States; D000077334:Zolpidem
chemical_list: D000081:Acetamides; D053961:Azabicyclo Compounds; D065692:Cytochrome P-450 CYP3A Inhibitors; D006993:Hypnotics and Sedatives; D010879:Piperazines; D011725:Pyridines; D011743:Pyrimidines; D011963:Receptors, GABA-A; D014229:Triazolam; D000077334:Zolpidem; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C085665:zaleplon; D000069582:Eszopiclone