Pharmacokinetics of diazepam during multiple dosing of a 6-mg controlled-release capsule once daily.

Sixteen subjects completed a two-way crossover study designed to determine the steady-state pharmacokinetic profiles of diazepam and desmethyldiazepam following a 6-mg controlled-release (CR) capsule dosed once daily compared with those of a 2-mg diazepam tablet dosed 3 times a day. Treatment A consisted of 14 days of CR dosing followed by 10 days of tablet dosing. Treatment B was the reverse of Treatment A. Plasma concentrations of diazepam and desmethyldiazepam were determined by an electron-capture gas-liquid chromatographic method. The areas under the diazepam plasma concentration-time curve were similar for both formulations at initiation of dosing and at steady-state, indicating comparable extents of absorption. The mean ratios of the areas at steady-state were near unity--0.94 for Treatment A and 0.91 for Treatment B--implying that no changes in steady-state conditions occurred upon switching regimens in either direction. The steady-state profiles of desmethyldiazepam were also comparable for the two dosage forms. These data indicate that the CR capsule and the conventional tablet t.i.d. produce similar target concentrations of both the drug and metabolite; therefore, these two dosage forms and dosing regimens should be interchangeable.