Pharmacokinetics and Distribution of Linezolid in Cerebrospinal Fluid in Children and Adolescents

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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 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.

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