Pharmacokinetics and distribution of linezolid in cerebrospinal fluid in children and adolescents

Ram Yogev*, Bharat Damle, Gweneth Levy, Sharon Nachman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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, C min, 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 μg/mL (range, 3.95-16.6 μg/mL) and 7.54 μg/mL (range, 2.26-12.6 μg/mL), respectively; mean Cmin values were 1.32 μg/mL (range, 0.08-3.66 μg/mL) and 1.26 μg/mL (range, 0.19-2.58 μg/mL), respectively. The VF:plasma ratio based on last dose AUC0-12 was 0.98 μg h/mL (range, 0.64-1.22 μg h/mL). In study 2, after the last dose, the mean plasma and VF Cmax levels were 9.83 μg/mL (range, 3.19-16.5 μg/mL) and 5.84 μg/mL (range, 1.82-9.34 μg/mL), respectively; mean plasma and VF Cmin levels were 1.12 μg/mL (range, 0.10-3.39 μg/mL) and 1.94 μg/mL (range, 0.34-4.62 μg/mL), respectively. The VF:plasma ratio based on last dose AUC0-8 was 0.95 μg h/mL (range, 0.62-1.31 μg 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.

Original languageEnglish (US)
Pages (from-to)827-830
Number of pages4
JournalPediatric Infectious Disease Journal
Volume29
Issue number9
DOIs
StatePublished - Sep 2010

Keywords

  • cerebrospinal fluid
  • children
  • linezolid
  • pharmacokinetics

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Microbiology (medical)
  • Infectious Diseases

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