Population pharmacokinetics of Phenytoin in critically ill children

Hennig, Stefanie, Norris, Ross, Tu, Quyen Tu, van Breda, Karin, Riney, Kate, Foster, Kelly, Lister, Bruce and Charles, Bruce (2014) Population pharmacokinetics of Phenytoin in critically ill children. Journal of Clinical Pharmacology, 55 3: 355-364. doi:10.1002/jcph.417


Author Hennig, Stefanie
Norris, Ross
Tu, Quyen Tu
van Breda, Karin
Riney, Kate
Foster, Kelly
Lister, Bruce
Charles, Bruce
Title Population pharmacokinetics of Phenytoin in critically ill children
Journal name Journal of Clinical Pharmacology   Check publisher's open access policy
ISSN 1552-4604
0091-2700
Publication date 2014-10-20
Year available 2014
Sub-type Article (original research)
DOI 10.1002/jcph.417
Open Access Status
Volume 55
Issue 3
Start page 355
End page 364
Total pages 10
Place of publication Hoboken, NJ, United States
Publisher Wiley-Blackwell Publishing
Collection year 2015
Language eng
Abstract The objective was to study the population pharmacokinetics of bound and unbound phenytoin in critical ill children, including influences on the protein binding profile. A population pharmacokinetic approach was used to analyse paired protein-unbound and total phenytoin plasma concentrations (n = 146 each) from 32 critically ill children (0.08 - 17 years of age) who were admitted to a paediatric hospital, primarily intensive care unit. The pharmacokinetics of unbound and bound phenytoin and the influence of possible influential covariates were modelled and evaluated using visual predictive checks and bootstrapping. The pharmacokinetics for protein-unbound phenytoin was described satisfactorily by a 1-compartment model with first-order absorption in conjunction with a linear partition coefficient parameter to describe the binding of phenytoin to albumin. The partitioning coefficient describing protein binding and distribution to bound phenytoin was estimated to be 8.22. Nonlinear elimination of unbound phenytoin was not supported in this patient group. Weight, allometrically scaled for clearance and volume of distribution for the unbound and bound compartments, and albumin concentration significantly influenced the partition coefficient for protein binding of phenytoin. The population model can be applied to estimate the fraction of unbound phenytoin in critically ill children given an individual's albumin concentration.
Keyword Phenytoin
Protein binding
Pharmacokinetics
Paediatrics
Critical care
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Accepted manuscript online: 20 OCT 2014

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
Official 2015 Collection
School of Pharmacy Publications
 
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Created: Tue, 21 Oct 2014, 12:06:57 EST by Dr Stefanie Hennig on behalf of School of Pharmacy