Source: Health Products Regulatory Authority (ZA) Publisher: CIPLA MEDPRO (PTY) LTD., Building 9, Parc du Cap, Mispel Street, Bellville, 7530
A.2.2. Sedatives, hypnotics
ATC Code: N05CF01
Zopiclone belongs to the chemical group the cyclopyrrolones, and is reported to have similar amnesic, anxiolytic, muscular relaxant, sedative and anti-convulsant properties to those of the benzodiazepines, although it is chemically distinct from them.
The pharmacological actions of zopiclone are mediated by the enhancement of the activity of aminobutyric acid (GABA) in the brain. It binds to the same receptor component of the GABA receptor in the brain as the benzodiazepines, but at a different site.
Zopiclone is rapidly absorbed. Peak concentration (30 to 60 mg/mL after doses of 3,75 mg) are reached within 1,5 to 2 hours. Absorption is not affected by co-administration with food.
Plasma protein binding is weak (approximately 45%) and non-saturable. Zopiclone is distributed into breastmilk, its concentration being approximately 50% that of plasma concentrations.
After repeated administration there is no accumulation of zopiclone and its metabolites Inter-individual variations appear to be low.
Zopiclone is extensively metabolised in humans to two major metabolites, N- oxide zopiclone (pharmacologically active in animals) and N-desmethyl zopiclone (pharmacologically inactive in animals). An in vitro study indicates that cytochrome P450 (CYPO 3A4 is the major isoenzyme involved in the metabolism of zopiclone to both metabolites, and that CYP2C8 is also involved with N-desmethyl zopiclone formation.
At recommended doses, the elimination half-life of the zopiclone is approximately 5 hours. Approximately 80% of zopiclone is eliminated renally, mainly in the form of free metabolites (N-oxide and N-demethyl derivations). Faecal elimination is approximately 16%.
In renal insufficiency, no accumulation of zopiclone or its metabolites has been detected after prolonged administration. Zopiclone is removed by haemodialysis.
In cirrhotic patients, the plasma clearance of zopiclone is reduced by approximately 40% in relation to the decrease of the demethylation process. Therefore, dosage will have to be modified in these patients.
In elderly patients, notwithstanding a slight decrease in hepatic metabolism and lengthening of elimination half-life to approximately 7-hour, various studies have not shown plasma accumulation of the medicine substance on repeated dosing.
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