Pharmacokinetics of N-desmethyldiazepam in healthy volunteers after single daily doses of dipotassium chlorazepate

Abstract

Dipotassium chlorazepate was administered to 12 healthy volunteers (8 males and 4 females), aged 22-38 years, as a single daily dose of 20 mg for 14 days. Plasma concentrations of N-desmethyldiazepam were monitored with a gas-chromatographic method during the medication period and for 5 days after withdrawal of the drug. The plasma half-life (t1/2), the elimination coefficient (Kbeta), the concentration (Css), and the apparent volume of distribution (Vbeta) were calculated at steady state, and the mean values +/- SEM were 53 +/- 6 h, 0.0147 +/- 0.0013 h-1, 884 +/- 73 ng/ml, and 1.13 +/- 0.08 1/kg, respectively. A moderate interindividual variability was observed regarding these parameters. There was no tendency toward a biexponential elimination. A significant difference in the apparent volume of distribution was found when males and females were compared.