Article date: April 1983
By: R Jochemsen, KL Nandi, D Corless, JG Wesselman, DD Breimer, in Volume 16, Issue S2, pages 299S-307S
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.
DOI: 10.1111/j.1365-2125.1983.tb02304.x
View this article