A Double-Blind Comparative Study of Three Formulations of Diazepam in Volunteers

Abstract

The sedation and subsequent recovery following administration of three formulations of diazepam (propylene glycol, mixed micelle and lipid emulsion) were compared in a randomised, double-blind, crossover study of twelve male volunteers. Following intravenous injections of 10 mg of each formulation, sedation was assessed for ten minutes using a six-point ordinal sedation score and subsequent recovery was assessed using a psychomotor/sedation battery including simple reflex time, letter deletion test, a simple arithmetic exercise, digit recall and a linear analogue sedation scale. Diazepam in propylene glycol was found to be more sedating that diazepam, either in a lipid formulation or as mixed micelles and appeared faster in its rise to peak effect than the lipid formulation. Subsequent recovery did not differ between the three groups. A significant increase in the level of sedation achieved by the preparations was found with each study day indicating that subject or testing factors were also important in determining the sedative response. Our results suggest that the new solvent systems, and in particular the lipid emulsion, primarily alter initial drug efficacy.