Pharmacokinetics of brotizolam in the elderly

Disposition of brotizolam in patients aged 71-93 years was compared with that of healthy young subjects aged 21-26 years. The mean elimination half-life of brotizolam was about twice as long in the elderly as in the young subjects: 9.3 (4.0-19.5) h and 4.8 (3.1-6.3) h respectively. Increase in elimination half-life was attributable to a decrease in hepatic clearance, i.e. 40 (20-58) ml/min in the elderly and 109 (77-156) ml/min in the young. Volume of distribution and protein binding were the same with mean values of 0.56 (0.45-0.72) l/kg and 9.0 (6.8-11.9) % in the elderly and 0.63 (0.40-0.77) l/kg and 8.4 (7.5-9.4) % in the young. Absorption rate of brotizolam was relatively slow in the elderly with a mean peak time of 1.7 h compared with 1.1 h in the young. Mean bioavailability was almost 70% for both groups. Normalized for body weight and dose (0.25 mg) mean peak concentrations were 247 (137-395) ng ml-1 kg in the young and 343 (251-446) ng ml-1 kg in the elderly. It is unlikely that substantial drug accumulation will occur if elderly patients ingest 0.25 mg brotizolam nightly.