Influence of cimetidine on oral diazepam elimination with measurement of subsequent cognitive change

In a double-blind crossover design, the effect of cimetidine on oral diazepam pharmacokinetics and an evaluation of cognitive function change was studied in seven healthy volunteers. Subjects randomly received placebo or cimetidine 300 mg orally every 6 h for a total of five doses prior to diazepam 10 mg. A significant increase in diazepam elimination half-life from (mean +/- s.e. mean) 66.9 +/- 21.4 to 89.6 +/- 22.5 h (P = 0.006) and area under the plasma concentration-time curve from 5.06 +/- 1.47 to 8.93 +/- 1.88 micrograms ml-1 h (P = 0.028) was observed indicating a probable cimetidine induced inhibition of diazepam hepatic metabolism. Digit symbol substitution and visual analogue scales were used to measure the effect of an alteration of diazepam kinetics on cognitive function. An enhancement of pharmacological effect as reflected in digit symbol substitution scores and visual analogue scale measurements was not observed.