Population pharmacokinetics of phenytoin in critically ill children

Article


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

Population pharmacokinetics of phenytoin in critically ill children

ERA Journal ID14791
Article CategoryArticle
AuthorsHennig, Stefanie (Author), Norris, Ross (Author), Tu, Quyen (Author), van Breda, Karin (Author), Riney, Kate (Author), Foster, Kelly (Author), Lister, Bruce (Author) and Charles, Bruce (Author)
Journal TitleThe Journal of Clinical Pharmacology
Journal of Clinical Pharmacology
Journal Citation55 (3), pp. 355-364
Number of Pages10
Year2014
Place of PublicationUnited States
ISSN0091-2700
1552-4604
Digital Object Identifier (DOI)https://doi.org/10.1002/jcph.417
Web Address (URL)https://accp1.onlinelibrary.wiley.com/doi/abs/10.1002/jcph.417
Abstract

The objective was to study the population pharmacokinetics of bound and unbound phenytoin in critically ill children, including influences on the protein binding profile. A population pharmacokinetic approach was used to analyze 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 pediatric hospital, primarily intensive care unit. The pharmacokinetics of unbound and bound phenytoin and the influence of possible influential covariates were modeled and evaluated using visual predictive checks and bootstrapping. The pharmacokinetics of 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.

Keywordscritical care; pediatrics; phenytoin; population pharmacokinetics; protein binding
ANZSRC Field of Research 2020429999. Other health sciences not elsewhere classified
Open access urlhttps://accp1.onlinelibrary.wiley.com/doi/abs/10.1002/jcph.417
Institution of OriginUniversity of Southern Queensland
ISBN15524604 00912700
Byline AffiliationsUniversity of Queensland
Griffith University
Mater Group, Australia
Department of Health, Queensland
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