Human and Animal Study on Elimination from Plasma and Metabolism of Diazepam after Chronic Alcohol Intake

Abstract: Very significantly lower concentrations of diazepam at 15 minutes and 1 hour after 10 mg intravenous diazepam injection were found in chronic alcoholic patients in comparison to healthy controls. Compared to 13 healthy controls a more rapid elimination of diazepam from the plasma of 14 chronic alcoholic patients during their alcohol‐free period was observed. The alcoholics had a smaller concentration of the diazepam main metabolite, N‐demethyl‐diazepam, and at 3 hours this difference was significant. The concentrations of free plasma oxazepam as a metabolite of diazepam, were not observed after a single dose of diazepam either in the alcoholics or in volunteers. A more rapid elimination of diazepam after 5 mg/kg intraperitoneally in the plasma of rats pretreated with ethyl alcohol (15% in drinking water for 3 weeks) was found than in the control rats. Pretreatment of rats with ethyl alcohol increased significantly the concentration of the hydroxylated metabolite, free oxazepam, in the plasma, but not of the demethylated metabolite, N‐demethyldiazepam.