This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Allegaert, K.
Right arrow Articles by Anderson, B. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Allegaert, K.
Right arrow Articles by Anderson, B. J.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, June 2008, p. 1934-1939, Vol. 52, No. 6
0066-4804/08/$08.00+0     doi:10.1128/AAC.01099-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Cerebrospinal Fluid Compartmental Pharmacokinetics of Amikacin in Neonates{triangledown}

K. Allegaert,1* I. Scheers,2 E. Adams,2 G. Brajanoski,1 V. Cossey,1 and B. J. Anderson3

Neonatal Intensive Care Unit, University Hospitals, Leuven, Belgium,1 Laboratorium voor Farmaceutische Chemie en Analyse van Geneesmiddelen, Faculteit, Farmaceutische Wetenschappen, Leuven, Belgium,2 Department of Anaesthesiology, University of Auckland, Auckland, New Zealand3

Received 21 August 2007/ Returned for modification 20 November 2007/ Accepted 22 March 2008

To describe and investigate the covariate effects of cerebrospinal fluid (CSF) amikacin pharmacokinetics in neonates, CSF samples were prospectively collected from neonates in whom amikacin had been initiated before a diagnostic lumbar puncture was performed. CSF analysis (amikacin concentration, white blood count [WBC], glucose content, and protein concentration) and amikacin therapeutic drug monitoring results (peak and trough concentrations) in serum were recorded. Correlations (Spearman rank) between the CSF amikacin concentration and the CSF WBC and glucose and protein concentration were investigated. There were 44 CSF amikacin concentrations and 83 serum samples available from 43 neonates (mean postmenstrual age, 36 weeks [range, 26 to 41 weeks]; mean weight, 2.43 kg [range, 0.87 to 3.86 kg]). The median time interval between initiation of amikacin administration and CSF sampling was 25 h (range, 2.5 to 93.7 h). The median amikacin concentration in the CSF was 1.08 mg/liter (range, 0.34 to 2.65 mg/liter), and the mean trough and peak amikacin concentrations in serum were 3.8 ± 2.5 mg/liter and 35.7 ± 5.9 mg/liter, respectively. A correlation between CSF amikacin and CSF protein contents (P < 0.01, r = 0.41, 95% confidence interval = 0.13 to 0.63) but not between CSF WBC and CSF glucose was documented. A two-compartment (central and CSF) linear disposition model was used to estimate population pharmacokinetics. The half time for equilibration (Teq) between serum and CSF compartments was used as a measure of blood-brain barrier permeability. The Teq was 7.58 h (coefficient of variation [CV] = 49.1%) with a partition coefficient of 0.103 (CV = 26.4%). There was no relationship between the Teq and CSF WBC, CSF glucose content, or CSF protein content.

* Corresponding author. Mailing address: Neonatal Intensive Care Unit, Division of Woman and Child, University Hospital, Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium. Phone: 32-16-343210. Fax: 32-16-343209. E-mail: karel.allegaert{at}uz.kuleuven.ac.be

{triangledown} Published ahead of print on 31 March 2008.

Antimicrobial Agents and Chemotherapy, June 2008, p. 1934-1939, Vol. 52, No. 6
0066-4804/08/$08.00+0     doi:10.1128/AAC.01099-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»