Clinical pharmacokinetics of midazolam in intensive care patients, a wide interpatient variability?

Clin Pharmacol Ther. 1988 Mar;43(3):263-9. doi: 10.1038/clpt.1988.31.


The pharmacokinetics of midazolam and its metabolites were studied in 17 patients on mechanical ventilation in a general intensive care unit who were receiving a continuous intravenous infusion of midazolam, adjusted according to the level of induced sedation. Three patients were studied twice. Serum midazolam and alpha-hydroxymidazolamglucuronide levels were determined during and after infusion. The sedation level was scored on a four-point scale. Half of the observed patients were still drowsy or asleep 10 hours after termination of midazolam infusion. In only one patient was midazolam serum elimination half-life less than 2 hours and in six patients the half-life was greater than 10 hours. A wide range of midazolam serum levels was associated with adequate sedation, and similarly the midazolam levels at the moment of awakening were highly variable. The serum concentration ratio of midazolam/alpha-hydroxymidazolamglucuronide at the end of the infusion varied from 0.03 to 15.6. Renal function could account for only a part of this variation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anesthesia, Intravenous*
  • Female
  • Glucuronates / metabolism
  • Half-Life
  • Humans
  • Male
  • Midazolam / administration & dosage
  • Midazolam / blood
  • Midazolam / pharmacokinetics*
  • Middle Aged
  • Pain Measurement
  • Respiration, Artificial*


  • Glucuronates
  • Midazolam