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  • Title: Linezolid in the central nervous system: comparison between cerebrospinal fluid and plasma pharmacokinetics.
    Author: Viaggi B, Paolo AD, Danesi R, Polillo M, Ciofi L, Del Tacca M, Malacarne P.
    Journal: Scand J Infect Dis; 2011 Sep; 43(9):721-7. PubMed ID: 21585240.
    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. 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.
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