Premium
Pharmacokinetics of diazepam from a controlled release capsule in healthy elderly volunteers
Author(s) -
Wills Robert J.
Publication year - 1984
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510050306
Subject(s) - pharmacokinetics , diazepam , capsule , half life , volume of distribution , population , crossover study , elimination rate constant , medicine , regimen , anesthesia , pharmacology , chemistry , placebo , botany , alternative medicine , environmental health , pathology , biology
A single dose open labelled two‐way randomized crossover study was used to assess the pharmacokinetics of diazepam from a controlled release capsule relative to standard release tablets in elderly volunteers. Eighteen volunteers received a single 15 mg controlled release capsule or a 5 mg tablet t.i.d. on one day. Diazepam plasma concentrations were determined at specific times over a 96‐h interval by an electron capture‐gas chromatographic method. Mean plateau plasma concentrations endured from 2 to 24h avoiding the peak to trough fluctuations associated with conventional t.i.d. dosing. Similar areas under the plasma concentration–time curve (AUC) values indicated equal extent of absorption between formulations and regimens. Comparing parameters in this same elderly population to a young adult population, previously administered the controlled release capsule, shows lower maximum concentrations and a longer plateau duration in the elderly volunteers. Although there is a twofold increase in the mean diazepam half‐life in the elderly when compared to young adults, the estimated apparent volume of distribution increased proportionately with half‐life to maintain a constant clearance. Thus, the total body clearance of diazepam appears to be age independent. The age‐dependent pharmacokinetics observed in this study are consistent with previously reported data involving diazepam. Overall, the controlled release capsule administered once daily mimics a t.i.d. regimen in elderly volunteeres.