Multiple-dose pharmacokinetics of diazepam following once-daily administration of a controlled-release capsule

The study was designed to determine the steady-state pharmacokinetic profile of diazepam and desmethyldiazepam following a 15-mg controlled-release capsule dosed once daily at either 7 a.m. or 11 p.m. compared with the respective profiles of the conventional 5-mg tablet dosed three times a day at 7 a.m., 12 p.m., and 5 p.m. Plasma concentrations of diazepam and desmethyldiazepam were assayed by an electron-capture gas-liquid chromatographic method. Plasma concentrations indicated that there were no differences between the pharmacokinetic profiles following the 7 a.m. or 11 p.m. dosings of the controlled-release capsule. Steady-state concentrations of diazepam were attained between days 7 and 9 during the controlled-release dosing, and the accumulation profiles are similar to those observed for the conventional tablet given three times a day. Nearly identical areas under the diazepam plasma concentration-time curves (AUC) on day 1 and at steady state for both regimens indicate equal extents of absorption from the two formulations. In addition, the steady-state AUCs for desmethyldiazepam were independent of formulation. The data indicate that a single daily dose of the 15-mg controlled-release capsule results in accumulation and steady-state profiles comparable to those observed following a regimen of the 5-mg conventional tablet three times a day.(ABSTRACT TRUNCATED AT 250 WORDS)