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

Abstract

1 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. 2 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. 3 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. 4 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. 5 There was poor correlation between the responses measured and the concentrations of either total diazepam, desmethyldiazepam or free diazepam. 6 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.

Psychoactive medication use, sensori‐motor function and falls in older women.

“…In a series of experimental trials, Swift et al have found that benzodiazepines impair reaction time and postural sway in elderly people [10,11]. In a previous case-control study of factors associated with injurious falls we also found associations between psychoactive medication use and quadriceps strength, postural sway and two clinical balance measures: static and dynamic balance [12].…”

Age‐related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications

“…Advancing age is also associated with increased sensitivity to the central nervous system effects of benzodiazepines [115]. Sedation is induced by diazepam at lower doses and lower plasma concentrations in elderly subjects [116,117]. Advancing age is also associated with increased sensitivity to the effects of nitrazepam, flurazepam, and loprazolam [118][119][120].…”

Development and validation of a 96-well equilibrium dialysis apparatus for measuring plasma protein binding

“…[1][2][3][4][5][6] Plasma proteins are major contributors to drug binding in blood. Therefore, to better understand the relationship between drug concentrations and pharmacological effects, one must determine the unbound fraction of the total drug concentration.…”