DISPOSITION OF 3 BENZODIAZEPINES AFTER SINGLE ORAL-ADMINISTRATION IN MAN

Abstract

Three benzodiazepines in equipotent doses: oxazepam 15 mg, dipotassium chlorazepate 10 mg and diazepam 5 mg, were administered in single, oral doses to 7 healthy volunteers in a 3-way cross-over study. The serum concentrations of oxazepam, N-desmethyldiazepam and diazepam were followed for 72 h 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 min, followed by N-desmethyldiazepam 80 min and oxazepam 114 min. The serum concentration decay curves were biphasic with terminal mean half-lives of 48, 62 and 11 h for diazepam, N-desmethyldiazepam and oxazepam, respectively. The mean and individual serum concentration time data were fitted to a 2-compartment open model with 1st 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 5 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 SD.