Abstract
Purpose
Antibacterial spectrum and activity of norvancomycin are comparable with vancomycin,
and it has been widely used in China. Norvancomycin can penetrate into the cerebrospinal
fluid (CSF) through the damaged blood–brain barrier in patients after craniotomy.
Because higher inter-individual variability was observed, we aimed to identify factors
related to drug concentration to guide clinicians with norvancomycin dosing.
Methods
After craniotomy, patients with an indwelling catheter in the operational area/ventricle
were intravenously administered norvancomycin. Venous blood and CSF specimens were
collected at a scheduled time for measuring drug concentrations. Blood and CSF data
were fitted simultaneously with the use of the nonlinear fixed-effects modeling method
to develop the population pharmacokinetic model. Covariate analysis was applied to
select candidate factors associated with pharmacokinetic parameters. A model-based
simulation was performed to find optimized regimens for different subgroups of patients.
Findings
A 3-compartmental model (central, peripheral, and CSF compartments) with 2 elimination
pathways (drug elimination from the kidney and CSF outflow) was developed to characterize
the in vivo process of norvancomycin. The covariate analysis identified that weight
and drainage amount were strongly associated with the central volume and the drug
clearance from CSF, respectively. Goodness-of-fit and model validation suggested that
the proposed model was acceptable. A dosage regimen table was created for specific
patient populations with different weights and drainage amounts to facilitate clinical
application.
Implications
We identified 2 clinical markers associated with plasma and CSF concentrations. The
proposed simulation may be useful to clinicians for norvancomycin dosing in this specific
population with normal kidney function.
Key words
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Article info
Publication history
Published online: December 08, 2017
Accepted:
November 13,
2017
Identification
Copyright
© 2017 Published by Elsevier Inc.
