TY - JOUR
T1 - Pharmacokinetics and distribution of linezolid in cerebrospinal fluid in children and adolescents
AU - Yogev, Ram
AU - Damle, Bharat
AU - Levy, Gweneth
AU - Nachman, Sharon
N1 - Funding Information:
Supported by Pfizer Inc.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2010/9
Y1 - 2010/9
N2 - 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.
AB - 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.
KW - cerebrospinal fluid
KW - children
KW - linezolid
KW - pharmacokinetics
UR - http://www.scopus.com/inward/record.url?scp=77955981228&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955981228&partnerID=8YFLogxK
U2 - 10.1097/INF.0b013e3181df4b9a
DO - 10.1097/INF.0b013e3181df4b9a
M3 - Article
C2 - 20442688
AN - SCOPUS:77955981228
SN - 0891-3668
VL - 29
SP - 827
EP - 830
JO - Pediatric Infectious Disease Journal
JF - Pediatric Infectious Disease Journal
IS - 9
ER -