Pharmacokinetics
After oral administration, zopiclone is rapidly absorbed, with a bioavailability of approximately 80%. The plasma protein binding of zopiclone has been reported to be between 45 and 80%. Zopiclone is rapidly and widely distributed to body tissues including the brain, and is excreted in urine, saliva and breast milk. Zopiclone is partly metabolised in the liver to form an inactive N-demethylated derivative and an active N-oxide metabolite. In addition, approximately 50% of the administered dose is decarboxylated and excreted via the lungs. In urine, the N-demethyl and N-oxide metabolites account for 30% of the initial dose. Between 7 and 10% of zopiclone is recovered from the urine indicating extensive metabolism of the drug before excretion. The terminal elimination half-life (t1/2z) of zopiclone ranges from 3.5 to 6.5 hours. The pharmacokinetics of zopiclone in humans are stereoselective. After oral administration of the racemic mixture, Cmax (time to maximum plasma concentration), AUC (area under the plasma time-concentration curve) and t1/2z values are higher for the dextrorotatory enantiomer owing to the slower total clearance and smaller volume of distribution (corrected by the bioavailability), compared with the levorotatory enantiomer. In urine, the concentrations of the dextrorotatory enantiomers of the N-demethyl and N-oxide metabolites are higher than those of the respective antipodes. The pharmacokinetics of zopiclone are altered by aging and are influenced by renal and hepatic functions.
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