Pharmacokinetics and sedative effect of midazolam in connection with caesarean section performed under epidural analgesia

Midazolam, the new investigational 1,4-benzodiazepine derivative with highly water-soluble salts, was studied as an anaesthesiological adjuvant in 11 patients undergoing elective caeserean section under epidural analgesia. I.v. administered midazolam, 0.075 mg/kg after delivery, caused a rapid and marked sedative effect, lasting for about 2-3 h. Short-lasting anterograde amnesia of about 30 to 60 min was reported as well. The serum levels of the parent drug and its active metabolites were determined in six cases by a radioreceptor assay and pharmacokinetic parameters were calculated on the basis of these levels by a two-compartment open model. Up to 3 h after midazolam administration, good correlation between the sedative effect and serum drug levels was found. The rapid but short-lasting action can be explained by the pharmacokinetic parameters of midazolam: a short distribution phase half-life (4.19 min), and a short elimination phase half-life (67.85 min) due to a high clearance value (13.18 ml/min/kg) and a moderate distribution volume (1.20 l/kg).