title: Linezolid in the central nervous system: comparison between cerebrospinal fluid and plasma pharmacokinetics.
abstract: BACKGROUND
  Linezolid is effective against methicillin-resistant Staphylococcus aureus, which may cause central nervous system (CNS) infections, but drug concentrations in plasma are characterized by a large inter-patient variability. Therefore, the present study was aimed at evaluating linezolid pharmacokinetics in plasma and cerebrospinal fluid (CSF) in 7 patients with external ventricular drainage, who received linezolid 600 mg twice daily as 1-h intravenous infusion to prevent CNS infections.
  
  
  METHODS
  Plasma and CSF linezolid concentrations were measured by high-performance liquid chromatography (HPLC) after the 1(st) and 5(th) dose, and pharmacokinetics were evaluated by non-compartmental analysis.
  
  
  RESULTS
  Values of the CSF area under the time/concentration curve (AUC) (range 18.2-85.5 and 19.6-160.5 h × mg/l at the 1st and 5th dose, respectively) were lower than those calculated in plasma (range 27.6-224.0 and 27.5-166.1 h × mg/l, respectively). For minimum inhibitory concentration (MIC) = 1 mg/l, CSF AUC/MIC values were nearly equal to or greater than 100 only in 2 subjects after the 1st and 5th dose, whereas mean time above the MIC (T > MIC) values were higher than 75% in only 3 patients. Similar results were obtained when pharmacokinetic/pharmacodynamic parameters were evaluated in plasma.
  
  
  CONCLUSIONS
  The present results suggest that changes in linezolid doses and measurement of drug concentrations should be considered as useful strategies to optimize treatment in some patients.
authors.affiliation: U.O. Anestesia e Rianimazione, Azienda Ospedaliera Universitaria Pisana, Via Roma 57, Pisa, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Viaggi
authors.forename: Antonello Di
authors.initials: AD
authors.lastname: Paolo
authors.forename: Romano
authors.initials: R
authors.lastname: Danesi
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Polillo
authors.forename: Laura
authors.initials: L
authors.lastname: Ciofi
authors.forename: Mario
authors.initials: M
authors.lastname: Del Tacca
authors.forename: Paolo
authors.initials: P
authors.lastname: Malacarne
mesh_terms: D000081:Acetamides / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001424:Bacterial Infections / Q000517:prevention & control; D002555:Cerebrospinal Fluid / Q000737:chemistry*; D002557:Cerebrospinal Fluid Shunts; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D000069349:Linezolid; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D023303:Oxazolidinones / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D010949:Plasma / Q000737:chemistry*; D013997:Time Factors
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D000069349:Linezolid