[Drug interactions of midazolam]

Midazolam is a short-acting benzodiazepine with a short half life (1.5-2.5 h) due to intense biotransformation by liver monooxygenases. Anecdotal clinical reports have mentioned a wide interpatient variability in its duration of action. We investigated by in vitro screening factors that could interfere with the rate of midazolam biotransformation (drug-drug interactions). Metabolite production (1'-and 4-OH-midazolam) was monitored in human liver microsomes. Midazolam hydroxylations are inhibited by several drugs (i.e. erythromycin, phenothiazine-type neuroleptics, cyclosporine). The clinical relevance of these drug interactions is illustrated by the example of a patient treated with amiodarone, erythromycin and midazolam during anesthesia. Midazolam-induced sleep lasted about 6 days due to inhibition of its biotransformation by concomitant drug treatment.