[Relation between the clinical effect and the pharmacokinetics of midazolam following i.m. and i.v. administration/2nd comm.: Pharmacokinetical aspects (author's transl)].

In a cross-over study 6 subjects were administered 12.5 mg 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a] [1,4]benzodiazepine (midazolam, Ro 21-3981, Dormicum) i.v. and i.m., with an interval of one week between the two applications. Midazolam, in the hydrochloride form, was administered by both the i.v. and i.m. route, and the lactate form only by the i.m. route. Determination of the concentration of midazolam in plasma was carried out by a gas chromatography method (Method ECD-GLC). After administration by i.m. route both salts were rapidly absorbed. The maximum concentrations were generally reached within 30 min after the injection. The mean absolute bioavailability is 91% for the hydrochloride and 82% for the lactate. The nature of the salts has no influence on bioavailability. On the basis of performance tests we obtained a good relation between the plasma concentration and the psychometric findings. 2--4 h after i.v. or i.m. administration the clinical effects are no longer measurable and the findings are approaching the initial values determined before the injection. The plasma concentration, on the other hand, is still measurable after the same lapse of time, at around 100 ng/ml.