Dose equivalence of midazolam and triazolam

Abstract

The pharmacodynamic potency of oral midazolam, a new ultrashort-acting hypnotic benzodiazepine, has been evaluated relative to a standard dose of triazolam, a well established oral benzodiazepine with a similar pharmacological profile. In a balanced design, double-blind cross-over study 6 healthy volunteers received 3.75, 7.5, and 15 mg midazolam and 0.25 mg triazolam orally, at 8 a.m., at weekly intervals. Drug effects were repeatedly measured over 8 h by a new psychometric method, the threshold amplitude for perception of flickering light (TPF) assessed at 5 and 30 Hz. Auditory reaction time, digit-symbol substitution test (DSST), and self-rating by subjects served as reference standards. Median midazolam doses equivalent to 0.25 mg triazolam, interpolated on dose-response curves for peak effects, were 5.2 mg (TPF 30 Hz), 6.4 mg (TPF 5 Hz), 6.5 mg (DSST), and 7.4 mg (reaction time), respectively. Alternative methods of data analysis gave similar results. Introduction of TPF as a highly reproducible and sensitive measure of the effect of benzodiazepines on the CNS offers new opportunities to compare the relative potencies of different benzodiazepines in man. Since clinical experience has shown 0.25 mg triazolam to be safe and effective, it is concluded that the corresponding single oral dose of midazolam is between 5 and 8 mg.