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 br...

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Bibliographic Details
Published in:Journal of pharmacy and pharmacology 2002-03, Vol.54 (3), p.335-340
Main Authors: Fernandez, Christine, Alet, Patrice, Davrinche, Catherine, Adrien, Joelle, Thuillier, Alain, Farinotti, Robert, Gimenez, François
Format: Article
Language:English
Subjects:
Administration, Oral
Animals
Area Under Curve
Azabicyclo Compounds
Biological and medical sciences
Brain - metabolism
Chromatography, High Pressure Liquid
Hypnotics and Sedatives - blood
Hypnotics and Sedatives - pharmacokinetics
Hypnotics. Sedatives
Male
Medical sciences
Neuropharmacology
Pharmacology. Drug treatments
Piperazines - blood
Piperazines - pharmacokinetics
Psychology. Psychoanalysis. Psychiatry
Psychopharmacology
Rats
Rats, Sprague-Dawley
Stereoisomerism
Tissue Distribution
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Summary: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.
ISSN:0022-3573
2042-7158
DOI:10.1211/0022357021778574