RT Journal Article
SR Electronic
T1 Pharmacokinetics of zopiclone and its enantiomers in Caucasian young healthy volunteers.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1125
OP 1128
VO 21
IS 6
A1 Fernandez, C
A1 Maradeix, V
A1 Gimenez, F
A1 Thuillier, A
A1 Farinotti, R
YR 1993
UL http://dmd.aspetjournals.org/content/21/6/1125.abstract
AB The disposition of the enantiomers of zopiclone and its two chiral metabolites was investigated after oral administration of a single dose of 15 mg of a racemic mixture (twice the usual therapeutic regimen) in 12 adult Caucasian volunteers. Determination of concentrations of zopiclone enantiomers in plasma showed that zopiclone pharmacokinetics is stereoselective with AUC0-->infinity values of 691.3 and 209.5 ng.ml-1.hr (p < 0.001), Cmax values of 87.3 and 44.0 ng.ml-1 (p < 0.001), oral CLtot/F values of 195.5 and 659.8 ml.min-1 (p < 0.001), Vd/F values of 98.6 and 192.8 liters (p < 0.01) and elimination half-life of 399.2 and 225.6 min (p < 0.01) for (+)-zopiclone and (-)-zopiclone, respectively. On the contrary, absorption half-life and Tmax values were not significantly different. In 48-hr urine, 3.6% of unchanged zopiclone was excreted, whereas 14.2% and 13.8% of both metabolites, N-desmethylzopiclone and N-oxidezopiclone, respectively, were found. Quantities of (+)-zopiclone excreted in urine were always higher compared with its antipode (-)-zopiclone for the 12 volunteers (p < 0.001). For the metabolites, quantities of both enantiomers were either equal or different and when different, it was always in favor of the (+)-enantiomer.