title: Effect of severity of sepsis on tissue concentrations of linezolid.
abstract: OBJECTIVE
  In the present study, we examined whether differences in the severity of sepsis translate to differences in the pharmacokinetic profile of linezolid in plasma and the interstitium of target tissues after a single intravenous dose of 600 mg by means of the microdialysis technique.
  
  
  METHODS
  A total of 24 patients were included in the trial. Sixteen patients suffered from septic shock and eight patients presented with severe sepsis. Sepsis was diagnosed and verified according to the criteria of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee. Historic data derived from a previous study determining the pharmacokinetic profiles of linezolid in tissues and plasma in young healthy volunteers served as controls.
  
  
  RESULTS
  In the present study, the AUC for free linezolid from 0 to 24 h (fAUC(0-24)) ranged from 50 to 71 mg x h/L after single-dose administration in patients presenting with severe sepsis or septic shock. The mathematically extrapolated fAUC(0-24) ranged from 100 to 146 mg x h/L for twice-daily administration and a dosing interval of 12 h. No statistically significant difference in key pharmacokinetic parameters was detected between patients suffering from severe sepsis and septic shock (P > 0.05).
  
  
  CONCLUSIONS
  These data indicated that the severity of sepsis has no substantial effect on the pharmacokinetic profile of linezolid in plasma and in the interstitium of soft tissues.
authors.affiliation: Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
authors.forename: Christiane
authors.initials: C
authors.lastname: Thallinger
authors.forename: Cornelia
authors.initials: C
authors.lastname: Buerger
authors.forename: Nele
authors.initials: N
authors.lastname: Plock
authors.forename: Sascha
authors.initials: S
authors.lastname: Kljucar
authors.forename: Sonja
authors.initials: S
authors.lastname: Wuenscher
authors.forename: Robert
authors.initials: R
authors.lastname: Sauermann
authors.forename: Charlotte
authors.initials: C
authors.lastname: Kloft
authors.forename: Christian
authors.initials: C
authors.lastname: Joukhadar
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000273:Adipose Tissue / Q000378:metabolism*; D000284:Administration, Oral; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007275:Injections, Intravenous; D000069349:Linezolid; D017551:Microdialysis; D018482:Muscle, Skeletal / Q000378:metabolism*; D023303:Oxazolidinones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism; D012720:Severity of Illness Index; D014018:Tissue Distribution
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D000069349:Linezolid