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Cerebrospinal fluid compartmental pharmacokinetics of amikacin in neonates

Abstract number: P1246

Allegaert K., Scheers I., Adams E., Brajanoski G., Cossey V., Anderson B.J.

Objectives: To describe and investigate covariate effects (leukocytosis, glycorrhachia, protein concentration) on cerebrospinal fluid (CSF) pharmacokinetics of amikacin in neonates.

Methods: 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, glucose content, protein concentration) and amikacin therapeutic drug monitoring results (peak and trough concentrations) in plasma were recorded. A two compartment (central and CSF) linear disposition model was used to estimate population pharmacokinetics. The half-time (Teq) for equilibration between plasma and CSF compartments was used as a measure of blood brain barrier permeability.

Results: Based on 44 CSF amikacin concentrations and 83 plasma samples available from 43 neonates, data analysis revealed two distinct groups of neonates: those with a very short Teq (0.155 SD 0.024 h) and those with a long Teq (67.9 SD 22.5 h). A white cell count above 21 cells per mm3 in the CSF was associated with a low Teq while no relationship between Teq and CSF glucose or protein could be established.

Conclusions: There is important between individual variability in Teq following amikacin administration in neonates that is associated with CSF WBC. The impact of CSF WBC on amikacin Teq is of potential relevance for both effectiveness and ototoxicity of this drug in neonates.

Session Details

Date: 19/04/2008
Time: 00:00-00:00
Session name: 18th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Barcelona, Spain
Presentation type:
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