Metabolism of loprazolam in rat- and dog-liver preparations

Abstract

1. The metabolism of loprazolam by rat- and dog-liver preparations has been studied in aerobic and anaerobic conditions. Identification of unchanged loprazolam and metabolites was by comparison of chromatographic characteristics and mass spectra with those of authentic compounds.

2. The piperazine-N-oxide was the sole metabolite formed under aerobic conditions in dog-liver slices and microsomes.

3. In addition to this N-oxide, the N-desmethyl metabolite and the diazepine-hydroxy metabolite were formed in rat-liver microsomes. The principal metabolite in rat-liver slices was the glucuronide of the hydroxy compound.

4. Under anaerobic conditions the nitro group of loprazolam is reduced to the amine by dog-liver slices and rat-liver microsomes.