Responsiveness to oral diazepam in the elderly: relationship to total and free plasma concentrations

The immediate and residual response to single doses of oral diazepam 10 mg was measured in 11 young and 12 elderly healthy volunteers using postural sway, digit symbol substitution scores and subjective ratings. The effect on postural sway was markedly accentuated in the older volunteers, but the difference between groups in the effect on the other measures used did not achieve significance. The corresponding plasma total diazepam concentrations were lower in the older subjects beyond 0.5 h post dose and the concentrations of plasma desmethyldiazepam did not differ between the groups. Diazepam plasma protein binding was significantly reduced in the elderly subjects, but the plasma free (unbound) diazepam concentrations did not exceed those in the young group. There was poor correlation between the responses measured and the concentrations of either total diazepam, desmethyldiazepam or free diazepam. The results suggest the occurrence of a non-uniform effect of age on different aspects of benzodiazepine response, and that where an accentuated effect occurs the mechanisms are substantially pharmacodynamic.