Temazepam clearance unaltered in cirrhosis.
The kinetics of a single oral dose of the benzodiazepine hypnotic temazepam was evaluated in nine patients with biopsy-proven cirrhosis and in seven healthy controls matched for age and sex. Peak serum temazepam concentrations were reached later in cirrhotics than in controls (2.9 versus 0.6 h after dosage; p less than 0.05), indicating slower temazepam absorption in patients with cirrhosis. Temazepam volume of distribution was smaller in cirrhotics compared to controls, and elimination half-life shorter (10.6 versus 14.6 h). However, these differences were not significant. There were no significant differences between cirrhotics and controls in clearance of total temazepam (1.03 versus 1.03 ml/min/kg), clearance of unbound temazepam (27 versus 31 ml/min/kg), or free fraction in serum (3.9 versus 3.5% unbound). In two cirrhotic patients who received 20 mg of temazepam daily for 8 days, the extent of accumulation was consistent with the dosage interval relative to the elimination half-life, and was similar to the accumulation profile in healthy volunteers. Thus the onset of temazepam hypnotic activity may be delayed in cirrhotic patients, but the rate of elimination and the extent of accumulation are not altered compared to healthy persons of similar age and sex.
Ochs
H R
HR
Greenblatt
D J
DJ
Verburg-Ochs
B
B
Matlis
R
R
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D014151:Anti-Anxiety Agents / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D008103:Liver Cirrhosis / Q000378:metabolism*; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D013693:Temazepam / Q000008:administration & dosage / Q000378:metabolism*
D014151:Anti-Anxiety Agents; D013693:Temazepam