title: Clinical pharmacokinetics of midazolam in intensive care patients, a wide interpatient variability?
abstract: 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.
authors.affiliation: Medisch Centrum Alkmaar, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Oldenhof
authors.forename: M
authors.initials: M
authors.lastname: de Jong
authors.forename: A
authors.initials: A
authors.lastname: Steenhoek
authors.forename: R
authors.initials: R
authors.lastname: Janknegt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000771:Anesthesia, Intravenous; D005260:Female; D005965:Glucuronates / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D008297:Male; D008874:Midazolam / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged; D010147:Pain Measurement; D012121:Respiration, Artificial
chemical_list: D005965:Glucuronates; D008874:Midazolam