Induction Effect of Diazepam on its Own Metabolism

Abstract

Abstract: In the 7 psychiatric patients 10 mg diazepam administered intravenously, during continuous therapy, caused a significantly lower increase of diazepam concentrations in the plasma (at 15 min. P < 0.01; 1 hour P < 0.001; 3 and 6 hours P < 0.05; 24 hours P < 0.001) than in 13 healthy volunteers as an indicator of the increased elimination rate of diazepam. As a sign of the increased formation of the main metabolite, the increase in the concentration of N‐demethyldiazepam was significantly higher in the psychiatric patients on continuous diazepam therapy (at 15 min. P < 0.05; 1 hour P < 0.01) than in healthy volunteers. The intravenous injection of 10 mg diazepam caused in 7 psychiatric patients on continuous diazepam therapy a significantly lower mean increase of diazepam concentrations in the plasma (at 15 min., 1 hour, 3 and 6 hours P < 0.01; 24 hours P < 0.001) than in 12 psychiatric patients treated without diazepam and significantly higher increase in the concentrations of N‐demethyldiazepam (at 1 hour P < 0.05). No measurable amounts of free oxazepam was found in the plasma.