Plasma concentrations and central nervous system effects of the new hypnotic agent zopiclone in patients with chronic liver disease.
Eight healthy individuals and seven cirrhotic patients received 7.5 mg zopiclone orally. Two further cirrhotics received 3.75 mg. Plasma concentrations of zopiclone and psychometric tests including reaction time and critical flicker fusion threshold and electroencephalographic tracings were performed at regular intervals after drug administration. Peak plasma levels of zopiclone were similar in the two groups but the time to peak was delayed in the cirrhotics. Plasma zopiclone half-life was 8.53 +/- 0.83 h in the cirrhotics and 3.50 +/- 0.33 h in the healthy individuals. In the group of cirrhotics there was a negative correlation between zopiclone half-life and serum albumin concentration (r = -0.87). Zopiclone caused sedation in both groups. Reaction time was prolonged and critical flicker fusion threshold reduced in both groups. Recovery was delayed in the cirrhotics compared to the healthy subjects but was complete by 8 h. The size of the changes was somewhat greater in the cirrhotics but baseline observations differed between the groups. The mean dominant frequency was lower in the cirrhotics and fell slightly in that group after zopiclone administration. The response to zopiclone is delayed and exaggerated in cirrhosis. Precautions are therefore required when using this drug in patients with chronic liver disease.
D000328:Adult; D000368:Aged; D053961:Azabicyclo Compounds; D002492:Central Nervous System Depressants; D002908:Chronic Disease; D004569:Electroencephalography; D005260:Female; D005425:Flicker Fusion / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D006993:Hypnotics and Sedatives / Q000378:metabolism*; D007700:Kinetics; D008103:Liver Cirrhosis / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000378:metabolism* / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects
D053961:Azabicyclo Compounds; D002492:Central Nervous System Depressants; D006993:Hypnotics and Sedatives; D010879:Piperazines; C515050:zopiclone