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Disposition of three benzodiazepines after single oral administration in man.

Three benzodiazepines in equipotent doses: oxazepam 15 mg, dipotassium chlorazepate 10 mg and diazepam 5 mg, were administered in single, oral doses to seven healthy volunteers in a three-way cross-over study. The serum concentrations of oxazepam, N-desmethyldiazepam and diazepam were followed for 72 hours by gas chromatography and electron capture detection. The absorption of diazepam was most rapid and the mean time required to reach peak serum concentration was 45 minutes, followed by N-desmethyldiazepam 80 minutes and oxazepam 114 minutes. The serum concentration decay curves were biphasic with terminal mean half-lives of 48, 62 and 11 hours for diazepam, N-desmethyldiazepam and oxazepam, respectively. The mean and individual serum concentration time data were fitted to a two-compartment open model with first order absorption using a non linear least square program. The mean serum data fitted the model well. The same rank order was obtained with mean absorption half-lives as when comparing mean peak times while slightly shorter terminal half-lives were obtained in the curve fitting of mean serum data. Due to irregularities in the serum concentration time curves only five out of the 21 sets of individual data could satisfy the convergence criterion. The obtained parameters in the curve fitting were also accompanied with very large asymptotic standard deviations.