Pharmacokinetics of midazolam and alfentanil in outpatient general anesthesia. A study with concomitant thiopentone, flumazenil or placebo administration.

The pharmacokinetics of alfentanil, midazolam and thiopentone used for induction of short general anaesthesia were studied in 55 gynaecological outpatients. All the patients received midazolam as premedication. The patients received intravenous anaesthesia with alfentanil and either thiopentone or midazolam, supplemented with either nitrous oxide or air in oxygen ventilation, reversed by the end of anaesthesia with either placebo or flumazenil. Blood sampling for serum concentration measurements of midazolam, alfentanil and thiopentone was performed regularly for 7 h. The following mean pharmacokinetic parameters (mean +/- s.e. mean) were calculated for midazolam and alfentanil, respectively: elimination half-life 3.9 +/- 0.3 h and 1.2 +/- 0.05 h, apparent volume of distribution 107 +/- 61 and 31 +/- 1.5 l, total body clearance 20 +/- 0.7 l/h and 18 +/- 0.8 l/h. No influence of flumazenil on the kinetics of midazolam and no influence of thiopentone, midazolam, flumazenil or nitrous oxide on the kinetics of alfentanil was found. The serum levels of thiopentone were below the detection limit of the assay after 60 min, which made an evaluation of pharmacokinetic parameters impossible. Significant positive correlations were found in the individual patient between midazolam and alfentanil for all pharmacokinetic variables evaluated. For midazolam, an increase in the elimination half-life and the apparent volume of distribution was positively correlated to an increase of body-weight. For alfentanil, a decrease in the total body clearance and an increase in the elimination half-life were positively correlated to an increase of age. A prolonged elimination half-life of alfentanil was positively correlated to use of alcohol. High serum levels of thiopentone were positively correlated to increasing age of the patients.