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 1^st and 5^th 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 1^st and 5^th 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. Conclusion: 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.

Keywords::

• Linezolid
• pharmacokinetics
• central nervous system
• cerebrospinal fluid
• PK/PD

Acknowledgements

The authors wish to thank the nursing staff for their valuable help in performing the study.

Declaration of Interest: No financial support was received to perform the present study, and the authors have no potential conflict of interest to declare.