Pharmacokinetics of zopiclone and its enantiomers in Caucasian young healthy volunteers.
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.
Fernandez
C
C
Hôpital Pitié Salpêtrière, Service Pharmacie-Pharmacocinétique, Paris, France.
Maradeix
V
V
Gimenez
F
F
Thuillier
A
A
Farinotti
R
R
D000284:Administration, Oral; D000328:Adult; D053961:Azabicyclo Compounds; D006801:Humans; D006993:Hypnotics and Sedatives / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D010879:Piperazines / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D013237:Stereoisomerism; D044465:White People
D053961:Azabicyclo Compounds; D006993:Hypnotics and Sedatives; D010879:Piperazines; C515050:zopiclone; C053228:zopiclone N-oxide; C053229:N-desmethylzopiclone