Population pharmacokinetics of phenytoin in critically ill children

Hennig, Stefanie and Norris, Ross and Tu, Quyen and van Breda, Karin and Riney, Kate and Foster, Kelly ORCID: https://orcid.org/0000-0002-3328-2177 and Lister, Bruce and Charles, Bruce (2014) Population pharmacokinetics of phenytoin in critically ill children. Journal of Clinical Pharmacology, 55 (3). pp. 355-364. ISSN 0091-2700


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.


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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Faculty/School / Institute/Centre: No Faculty
Faculty/School / Institute/Centre: No Faculty
Date Deposited: 10 Dec 2020 05:23
Last Modified: 10 Dec 2020 05:23
Uncontrolled Keywords: critical care; pediatrics; phenytoin; population pharmacokinetics; protein binding
Fields of Research (2008): 11 Medical and Health Sciences > 1115 Pharmacology and Pharmaceutical Sciences > 111502 Clinical Pharmacology and Therapeutics
Fields of Research (2020): 42 HEALTH SCIENCES > 4299 Other health sciences > 429999 Other health sciences not elsewhere classified
Identification Number or DOI: https://doi.org/10.1002/jcph.417
URI: http://eprints.usq.edu.au/id/eprint/40326

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