[A microprocessor controlled infusion scheme for midazolam to achieve constant plasma levels (author's transl)]

In seven healthy volunteers a microprocessor controlled Infusion scheme for midazolam was established on the basis of pharmacokinetic analysis. The dosage regimen is composed of three different parts (BET-infusion): 1. a bolus initially injected for filling the central compartment 2. the elimination rate compensating the drug loss by elimination and 3. the transfer rate exponentially declining and balancing midazolam transfer to the peripheral compartment. --Thus, the amount of drug necessary for well-defined plasma levels can be minimized compared with other optimized dosage regimens like repetitive boluses or combinations of different infusion rates. By using this BET-infusion technique we were able to attain nearly constant therapeutic plasma levels from the beginning on (without initial overshoot). Unwanted cardiovascular and respiratory side effects could be prevented. The median of EEG-power spectra was used for monitoring EEG-background activity and for the correlation of plasma levels and pharmacological effect. The minimal plasma level producing a deep hypnotic effect with an EEG-median of less than 5 s-1 was about 0.5 microgram/ml. On the basis of these findings several modes of dosage are presented obtaining at least therapeutic midazolam concentrations of 0.6 microgram/ml for a secure hypnotic effect.