Comparisons of Four Protein-Binding Models Characterizing the Pharmacokinetics of Unbound Phenytoin in Adult Patients Using Non-Linear Mixed-Effects Modeling.

ABSTRACT:

Background and objective

Phenytoin is extensively protein bound with a narrow therapeutic range. The unbound phenytoin is pharmacologically active, but total concentrations are routinely measured in clinical practice. The relationship between free and total phenytoin has been described by various binding models with inconsistent findings. Systematic comparison of these binding models in a single experimental setting is warranted to determine the optimal binding behaviors.

Methods

Non-linear mixed-effects modeling was conducted on retrospectively collected data (n = 37 adults receiving oral or intravenous phenytoin) using a stochastic approximation expectation-maximization algorithm in MonolixSuite-2019R2. The optimal base structural model was initially developed and utilized

SUBMITTER: Jun H 

PROVIDER: S-EPMC7691416 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature