title: Decreased plasma albumin concentration results in increased volume of distribution and decreased elimination of midazolam in intensive care patients.
abstract: The pharmacokinetic parameters of 16 patients in the intensive care unit, sedated with midazolam, were evaluated. A large variation was observed in the plasma concentration of midazolam and between the plasma concentration of midazolam and its metabolite 1-hydroxymethylmidazolam glucuronide. The plasma albumin concentration governs the volume of distribution of midazolam. Decreased plasma albumin concentration (25 gm/L) results in an increased volume of distribution and a decreased elimination rate of midazolam. The observed plasma concentration ratio between the parent drug and its metabolite 1-hydroxymethylmidazolam glucuronide is governed by the variables of protein binding, the metabolic rate of midazolam, and the renal clearance of the glucuronide metabolite itself (which can be considered as a measure of the kidney function of the patient).
authors.affiliation: Department of Clinical Pharmacy, Sint Radboud Hospital, University of Nijmegen, The Netherlands.
authors.forename: T B
authors.initials: TB
authors.lastname: Vree
authors.forename: M
authors.initials: M
authors.lastname: Shimoda
authors.forename: J J
authors.initials: JJ
authors.lastname: Driessen
authors.forename: P J
authors.initials: PJ
authors.lastname: Guelen
authors.forename: T J
authors.initials: TJ
authors.lastname: Janssen
authors.forename: E F
authors.initials: EF
authors.lastname: Termond
authors.forename: R
authors.initials: R
authors.lastname: van Dalen
authors.forename: J C
authors.initials: JC
authors.lastname: Hafkenscheid
authors.forename: M S
authors.initials: MS
authors.lastname: Dirksen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003422:Critical Care; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D016018:Least-Squares Analysis; D008297:Male; D008874:Midazolam / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged; D011485:Protein Binding; D012709:Serum Albumin / Q000032:analysis*
chemical_list: D012709:Serum Albumin; C061795:1-hydroxymethylmidazolam glucuronide; D008874:Midazolam