title: Pharmacokinetics and distribution of linezolid in cerebrospinal fluid in children and adolescents.
abstract: BACKGROUND
  Two studies in hydrocephalic children and adolescents were performed to assess the penetration of linezolid into cerebrospinal fluid and its relation to meningeal inflammation.
  
  
  METHODS
  Each patient was administered intravenous linezolid 10 mg/kg every 12 hours for 3 days (study 1) or every 8 hours for 2 days (study 2). Pharmacokinetic indices (Cmax, Cmin, Tmax, AUC) were determined for plasma and ventricular fluid (VF) after the first and last doses.
  
  
  RESULTS
  In study 1, after the last dose, the mean Cmax values for plasma and VF were 10.30 microg/mL (range, 3.95-16.6 microg/mL) and 7.54 microg/mL (range, 2.26-12.6 microg/mL), respectively; mean Cmin values were 1.32 microg/mL (range, 0.08-3.66 microg/mL) and 1.26 microg/mL (range, 0.19-2.58 microg/mL), respectively. The VF:plasma ratio based on last dose AUC0-12 was 0.98 microg h/mL (range, 0.64-1.22 microg h/mL). In study 2, after the last dose, the mean plasma and VF Cmax levels were 9.83 microg/mL (range, 3.19-16.5 microg/mL) and 5.84 microg/mL (range, 1.82-9.34 microg/mL), respectively; mean plasma and VF Cmin levels were 1.12 microg/mL (range, 0.10-3.39 microg/mL) and 1.94 microg/mL (range, 0.34-4.62 microg/mL), respectively. The VF:plasma ratio based on last dose AUC0-8 was 0.95 microg h/mL (range, 0.62-1.31 microg h/mL). Inflammation of the meninges did not seem to influence penetration of linezolid to the VF.
  
  
  CONCLUSIONS
  : Both studies showed that VF concentrations were variable. Further investigation of the role of linezolid in the treatment of CNS infection is needed.
authors.affiliation: Department of Pediatrics, Northwestern University Medical School, Chicago, IL, USA. RYogev@childrensmemorial.org
authors.forename: Ram
authors.initials: R
authors.lastname: Yogev
authors.forename: Bharat
authors.initials: B
authors.lastname: Damle
authors.forename: Gweneth
authors.initials: G
authors.lastname: Levy
authors.forename: Sharon
authors.initials: S
authors.lastname: Nachman
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002552:Cerebral Ventricles / Q000737:chemistry; D002555:Cerebrospinal Fluid / Q000737:chemistry*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D006849:Hydrocephalus; D007223:Infant; D007275:Injections, Intravenous; D000069349:Linezolid; D008297:Male; D023303:Oxazolidinones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010949:Plasma / Q000737:chemistry; D055815:Young Adult
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D000069349:Linezolid