A Comprehensive Review on the Predictive Performance of the Sheiner-Tozer and Derivative Equations for the Correction of Phenytoin Concentrations

The Annals of Pharmacotherapy
Tony K L Kiang, Mary H H Ensom

Abstract

In settings where free phenytoin concentrations are not available, the Sheiner-Tozer equation-Corrected total phenytoin concentration = Observed total phenytoin concentration/[(0.2 × Albumin) + 0.1]; phenytoin in µg/mL, albumin in g/dL-and its derivative equations are commonly used to correct for altered phenytoin binding to albumin. The objective of this article was to provide a comprehensive and updated review on the predictive performance of these equations in various patient populations. A literature search of PubMed, EMBASE, and Google Scholar was conducted using combinations of the following terms: Sheiner-Tozer, Winter-Tozer, phenytoin, predictive equation, precision, bias, free fraction. All English-language articles up to November 2015 (excluding abstracts) were evaluated. This review shows the Sheiner-Tozer equation to be biased and imprecise in various critical care, head trauma, and general neurology patient populations. Factors contributing to bias and imprecision include the following: albumin concentration, free phenytoin assay temperature, experimental conditions (eg, timing of concentration sampling, steady-state dosing conditions), renal function, age, concomitant medications, and patient type. Although deriva...Continue Reading

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Citations

Jul 4, 2019·British Journal of Clinical Pharmacology·Rob Ter HeineErik M van Maarseveen
Dec 24, 2019·Journal of Pharmacy Practice·Amanda Z WiebeJohn Skaggs
Sep 11, 2020·The Annals of Pharmacotherapy·Brian L Erstad
Apr 10, 2021·British Journal of Clinical Pharmacology·Arushi MadanCecilie M Lander

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