Stereoselective distribution and stereoconversion of zopiclone enantiomers in plasma and brain tissues in rats.
Concentrations of (-)-zopiclone and (+)-zopiclone were determined in plasma and brain after oral administration, to investigate the stereoselectivity of distribution in rats. Zopiclone enantiomers were administered separately to rats and concentrations were determined by chiral HPLC in plasma and brain. In initial experiments, rats were treated with urethane before cannulation for blood sampling but as this drug modified zopiclone pharmacokinetics, it was not used in subsequent studies. This study showed that zopiclone pharmacokinetics after oral gavage in rats are stereoselective. After oral administration of (+)-zopiclone, no stereoconversion was observed in plasma. Conversely, after administration of (-)-zopiclone, both enantiomers were found in plasma and brain with (+)-zopiclone/(-)-zopiclone ratios of 1 and 8.4 in plasma and brain, respectively. Our findings suggest that zopiclone undergoes stereoconversion and that it is stereospecifically distributed to the brain.
Fernandez
Christine
C
Faculty of Pharmacy, Clinical Pharmacy Department, UPRES EA 2706, Chatenay-Malabry, France. christine.fernandez@psl.ap-hop-paris.fr
Alet
Patrice
P
Davrinche
Catherine
C
Adrien
Joelle
J
Thuillier
Alain
A
Farinotti
Robert
R
Gimenez
François
F
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D053961:Azabicyclo Compounds; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006993:Hypnotics and Sedatives / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D010879:Piperazines / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D014018:Tissue Distribution
D053961:Azabicyclo Compounds; D006993:Hypnotics and Sedatives; D010879:Piperazines; C515050:zopiclone