title: Pharmacokinetics of linezolid in critically ill patients.
abstract: BACKGROUND
  Linezolid is an oxazolidinone antibiotic active against Gram-positive bacteria, and is most commonly used to treat life-threatening infections in critically ill patients. The pharmacokinetics of linezolid are profoundly altered in critically ill patients, partly due to decreased function of vital organs, and partly because life-sustaining drugs and devices may change the extent of its excretion.
  
  
  METHODS
  This article is summarizes key changes in the pharmacokinetics of linezolid in critically ill patients. The changes summarized are clinically relevant and may serve as rationale for dosing recommendations in this particular population.
  
  
  CONCLUSIONS
  While absorption and penetration of linezolid to tissues are not significantly changed in critically ill patients, protein binding of linezolid is decreased, volume of distribution increased, and metabolism may be inhibited leading to non-linear kinetics of elimination; these changes are responsible for high inter-individual variability of linezolid plasma concentrations, which requires therapeutic plasma monitoring and choice of continuous venous infusion as the administration method. Acute renal or liver failure decrease clearance of linezolid, but renal replacement therapy is capable of restoring clearance back to normal, obviating the need for dosage adjustment. More population pharmacokinetic studies are necessary which will identify and quantify the influence of various factors on clearance and plasma concentrations of linezolid in critically ill patients.
authors.affiliation: a Gynecology and Obstetrics, Faculty of Medical Sciences , University of Kragujevac , Kragujevac , Serbia.
authors.forename: Predrag
authors.initials: P
authors.lastname: Sazdanovic
authors.affiliation: b Pharmacology, Toxicology and Clinical Pharmacy, Faculty of Medical Sciences , University of Kragujevac , Kragujevac , Serbia.
authors.forename: Slobodan M
authors.initials: SM
authors.lastname: Jankovic
authors.affiliation: c Pharmacology and Toxicology, Faculty of Medical Sciences , University of Kragujevac , Kragujevac , Serbia.
authors.forename: Marina
authors.initials: M
authors.lastname: Kostic
authors.affiliation: a Gynecology and Obstetrics, Faculty of Medical Sciences , University of Kragujevac , Kragujevac , Serbia.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Dimitrijevic
authors.affiliation: d Clinical Pharmacy, Faculty of Medical Sciences , University of Kragujevac , Kragujevac , Serbia.
authors.forename: Srdjan
authors.initials: S
authors.lastname: Stefanovic
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016638:Critical Illness; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods; D006094:Gram-Positive Bacteria / Q000187:drug effects; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D000069349:Linezolid / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D017093:Liver Failure / Q000503:physiopathology; D051437:Renal Insufficiency / Q000503:physiopathology; D014018:Tissue Distribution
chemical_list: D000900:Anti-Bacterial Agents; D000069349:Linezolid
keywords: Linezolid; critically ill patients; pharmacokinetics; therapeutic drug monitoring