Urinary Elimination of Nitrazepam and its Main Metabolites

Abstract

Nitrazepam and its main metabolites, 7-aminonitrazepam and 7-acetamidonitrazepam, free and conjugated, were determined in human urine after a single 5 mg oral dose. The determinations were performed by GLC method using 63Ni-EC-detector for unchanged nitrazepam and N selective detector for metabolites. Unchanged nitrazepam was poorly eliminated through the kidneys (about 1% of the dose). Interindividual variation of total excreted urinary metabolites was large ranging between 848-4933 .mu.g (17-99% of the dose during 7 days). Of this amount conjugated metabolites compose 57%. Urinary half-lives of free and conjugated 7-aminonitrazepam were (mean and ranges) 44 (23-65) and 46 (25-69) h, and of 7-acetamidonitrazepam 12 (5-31) and 18 (5-46) h, respectively. Half-lives of excreted metabolite amounts did not correlate with any pharmacokinetic parameter of unchanged nitrazepam in serum.