The effects of age and chronic liver disease on the elimination of temazepam.
The pharmacokinetics of the newer 1, 4 benzodiazepine temazepam were evaluated in 16 healthy subjects aged 18-92 years and in 15 cirrhotic patients, to ascertain the effect of ageing and liver disease. The data were analysed both by classic two compartment and by non-compartmental methods. The mean elimination half-life in the control subjects was 15.5 h, considerably longer than previous estimates. No correlation was found between age and pharmacokinetic parameters. The cirrhotic group showed no statistically significant difference in the pharmacokinetic parameters nor in the urinary recovery of the dose from the control group. Temazepam plasma protein binding was assessed in a second group of 9 cirrhotics of similar severity to the main group and in matched controls. When these binding data were applied to the mean clearance data, a modest although not statistically significant, reduction in free drug clearance was observed in the cirrhotic group. This study adds further support to the observation that drugs which undergo ether glucuronidation have normal elimination patterns in patients with liver disease. Temazepam may prove to be a useful hypnotic sedative in patients with liver disease.
Ghabrial
H
H
Desmond
P V
PV
Watson
K J
KJ
Gijsbers
A J
AJ
Harman
P J
PJ
Breen
K J
KJ
Mashford
M L
ML
D000328:Adult; D000367:Age Factors; D000368:Aged; D014151:Anti-Anxiety Agents / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism; D005260:Female; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008103:Liver Cirrhosis / Q000378:metabolism*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D010076:Oxazepam / Q000097:blood; D011485:Protein Binding; D013693:Temazepam / Q000097:blood / Q000378:metabolism*
D014151:Anti-Anxiety Agents; D001798:Blood Proteins; D010076:Oxazepam; D013693:Temazepam