Pharmacokinetics of diazepam from a controlled release capsule in healthy elderly volunteers

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 24 h 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 volunteers.