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Decreased plasma albumin concentration results in increased volume of distribution and decreased elimination of midazolam in intensive care patients
Author(s) -
Vree Tom B,
Shimoda Minoru,
Driessen Jacques J,
Guelen Pieter J M,
Janssen Tom J,
Termond Emiel F S,
Dalen Roelof,
Hafkenscheid Jan C M,
Dirksen Marijcke S C
Publication year - 1989
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1989.182
Subject(s) - plasma volume , volume of distribution , albumin , midazolam , medicine , distribution (mathematics) , intensive care , serum albumin , plasma concentration , anesthesia , pharmacology , intensive care medicine , pharmacokinetics , mathematics , mathematical analysis , sedation
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). Clinical Pharmacology and Therapeutics (1989) 46, 537–543; doi: 10.1038/clpt.1989.182