Plasma concentrations and pharmacokinetics of midazolam during anaesthesia

Abstract

Midazolam and 1-hydroxymidazolam plasma concentrations have been monitored and pharmacokinetic parameters of midazolam estimated during anaesthesia induced and Maintained by its repeated injection according to two protocols (3 × 0.3 mg kg−1 at 45 min intervals or an induction dose of 0.3 mg kg−1 with maintenance doses of 0.15 mg kg−1 at 30 min intervals). Minimum plasma concentrations of midazolam measured just before each injection were 258.8 ± 108.4 ng ml−1 for the first protocol and 353.1 ± 55.2 ng ml−1 for the second protocol; maximum midazolam concentrations, measured 5 min after the last administration, were 1103.1 ± 237.9 ng ml−1 and 743.0 ± 103.2 ng ml−1, respectively, suggesting that a continuous infusion of midazolam after a loading dose should be better than repeated injections at keeping the concentration close to the sedative level of 400 ng ml−1. The estimated pharmacokinetic parameters were similar to those already published, except for the β elimination half-life of midazolam (3.24 ± 0.90 h for protocol 1 and 3.34 ± 1.47 h for protocol 2) which was slightly longer than that reported for single dose studies. The comparison of plasma determinations, obtained either by gas-liquid chromatography or by a radioreceptor assay technicjue, clearly showed that 1-hydroxymidazolam, even after repeated midazolam administration, was not present at a concentration sufficient to affect the overall pharmacological activity of the parent drug.