title: Pharmacokinetics of linezolid in septic patients with and without extended dialysis.
abstract: OBJECTIVE
  Linezolid is an option for the treatment of infections caused by multiresistant Gram-positive bacteria. The survival of critically ill patients with acute renal failure (ARF) can be improved by increasing the dose of renal replacement therapy. Extended (daily) dialysis (ED) is a new and important approach to renal replacement therapy in intensive care units. The aim of the study was to evaluate the pharmacokinetics of linezolid in septic patients without ED and on ED, respectively.
  
  
  METHODS
  We studied the pharmacokinetics of linezolid in adult intensive care patients with sepsis (n = 5) and anuric septic patients with ARF being treated with ED (n = 10). Linezolid 600 mg was administered intravenously twice daily. The pharmacokinetic parameters, their variability, and possible covariates were analyzed using NONMEM.
  
  
  RESULTS
  The pharmacokinetics of linezolid followed a two-compartment model with clearance (Cl) = 0.159 L h(-1) kg(-1) +/- 51% (population mean +/- interindividual variability), central volume of distribution (V(1)) = 0.273 L/kg +/- 21%, intercompartmental clearance (Q) = 0.369 L h(-1) kg(-1), and peripheral volume of distribution (V(2)) = 0.271 L/kg. The clearance in ED patients while on dialysis was increased by 3.5 L/h, and patients with liver transplantation/resection had their clearance reduced by 60%. Intra-individual variability was much smaller than inter-individual variability.
  
  
  CONCLUSIONS
  Our results suggest that linezolid pharmacokinetics in critically ill patients with ARF undergoing ED is not comparable to that in healthy subjects and patients without ARF. The best method of managing linezolid dosage in such a complex group of patients, whose physiology can vary daily, would be to use therapeutic drug monitoring.
authors.affiliation: Pharmacy Department, University Hospital of Heidelberg, Germany. stefanie.swoboda@med.uni-heidelberg.de
authors.forename: Stefanie
authors.initials: S
authors.lastname: Swoboda
authors.forename: Michael C
authors.initials: MC
authors.lastname: Ober
authors.forename: Christoph
authors.initials: C
authors.lastname: Lichtenstern
authors.forename: Soundos
authors.initials: S
authors.lastname: Saleh
authors.forename: Vedat
authors.initials: V
authors.lastname: Schwenger
authors.forename: Hans-Günther
authors.initials: HG
authors.lastname: Sonntag
authors.forename: Walter Emil
authors.initials: WE
authors.lastname: Haefeli
authors.forename: Georg
authors.initials: G
authors.lastname: Hempel
authors.forename: Torsten
authors.initials: T
authors.lastname: Hoppe-Tichy
authors.forename: Markus A
authors.initials: MA
authors.lastname: Weigand
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D058186:Acute Kidney Injury / Q000097:blood / Q000150:complications / Q000628:therapy*; D000368:Aged; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003422:Critical Care; D016903:Drug Monitoring; D005260:Female; D006498:Hepatectomy; D006801:Humans; D007262:Infusions, Intravenous; D000069349:Linezolid; D016031:Liver Transplantation; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D023303:Oxazolidinones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006435:Renal Dialysis / Q000379:methods*; D018805:Sepsis / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000081:Acetamides; D000890:Anti-Infective Agents; D023303:Oxazolidinones; D000069349:Linezolid