Importance of the interaction of midazolam and cimetidine

Six healthy volunteers were given in an open study 15 mg of midazolam orally, and a couple of weeks later the same treatment preceded by 400 mg of cimetidine orally. We followed midazolam serum concentrations and the following pharmacodynamic parameters for five hours: subjective sedation, Maddox wing readings, critical flicker fusion frequency and peak velocity of saccadic eye movements. A statistically significant change was found in Cmax and total AUC between the two sessions. The pharmacodynamic responses differed also clearly from each other suggesting a significant change in midazolam effect even after a single oral dose of cimetidine.