Decreased plasma albumin concentration results in increased volume of distribution and decreased elimination of midazolam in intensive care patients

Clin Pharmacol Ther. 1989 Nov;46(5):537-44. doi: 10.1038/clpt.1989.182.

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).

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Critical Care
  • Female
  • Humans
  • Infusions, Intravenous
  • Least-Squares Analysis
  • Male
  • Midazolam / administration & dosage
  • Midazolam / analogs & derivatives
  • Midazolam / blood
  • Midazolam / pharmacokinetics*
  • Middle Aged
  • Protein Binding
  • Serum Albumin / analysis*

Substances

  • Serum Albumin
  • 1-hydroxymethylmidazolam glucuronide
  • Midazolam