PHARMACOKINETICS OF INTRAVENOUS MIDAZOLAM DURING EPIDURAL-ANESTHESIA

Midazolam concentration curves versus time were analysed in 10 otherwise healthy patients (ASA I-II) with inferior limb pathologies. The benzodiazepine was used as an adjuvant agent to epidural anaesthesia in view of its lower residual effect compared with other intravenous benzodiazepines. Midazolam pharmacokinetics in these patients fitted an open two-compartment model. The plasma levels versus time corresponded to a biexponential process with a very rapid distribution phase (t1/2-alpha = 5.7 +/- 2.4 min) and an elimination phase (t1/2-beta = 66 +/- 37 min). Mean values for distribution volumes in the central compartment and extrapolated values were V(c) = 0.12 +/- 0.04 l/kg and V-beta = 1.28 +/- 0.92 l/kg. This kinetic behaviour explains the rapid but short duration of midazolam action. The induction time, estimated from the start of hypnosis (eye closure), was from 60 to 120 s with i.v. injection. The duration of action for the dose administered was from 15 to 60 min, with plasma levels below 90 ng/ml upon eye opening.