Biliary Excretion of Diazepam and its Metabolites in Man

Ten mg diazepam was given intravenously to 12 patients with a T‐tube in the common bile duct after choledochotomy (Group I) and to 10 patients after cholecystectomy (Group II). The concentrations of diazepam, of its main metabolite, N‐demethyldiazepam, and of free oxazepam in the plasma of both groups and the conjugated and free concentrations of diazepam, N‐demethyldiazepam, and oxazepam in the bile in the Group I were measured by gas chromatography. In Group I significantly lower plasma diazepam concentrations were obtained as compared with Group II indicating an enterohepatic circulation of diazepam. There was no significant difference in the concentrations of N‐demethyldiazepam in the plasma between the two groups. In Group I the patients had frequently more free oxazepam in their plasma than in Group II. The main conjugated metabolite in the bile was N‐demethyldiazepam (about 74 %). Traces of diazepam were in the conjugated form, but no conjugated oxazepam was found in the human bile. The enterohepatic circulation of diazepam and its metabolites may be partly responsible for the prolonged effects of diazepam.