ArticleTherapeutic drug monitoring2020
A Novel Correction Equation Avoids High-Magnitude Errors in Interpreting Therapeutic Drug Monitoring of Phenytoin Among Critically Ill Patients.
Article in Therapeutic drug monitoring, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 9 citations in OpenAlex.
- Antiseizure medication dosing and monitoring in the intensive care unit: a practical narrative review.Intensive care medicine · 2026Review
- Estimation of Free Phenytoin Concentration in Critically Ill Patients with Hypoalbuminemia: Direct-measurement vs Traditional Equations.Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine · 2022Article
- Therapeutic drug monitoring of phenytoin and valproic acid in critically ill patients at Windhoek Central Hospital, Namibia.African journal of laboratory medicine · 2022Article
- The Effect of Plasma Protein Binding on the Therapeutic Monitoring of Antiseizure Medications.Pharmaceutics · 2021Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPhenytoin has a narrow therapeutic index and the potential of under-treatment or toxicity. Available equations are used to correct for the impact of hypoalbuminemia on unbound (free) phenytoin levels. The authors aimed to determine the accuracy of equations used to estimate free phenytoin in hospitalized patients and assess the impact of using additional clinical data.
methodsConcurrently measured total and free phenytoin levels in hospitalized patients (2014-2018) were retrospectively evaluated, excluding those from patients on renal replacement therapy and valproic acid. Differences between actual and estimated free phenytoin levels by the original (Original WTZ), Anderson-modified, and Kane-modified Winter-Tozer equations were assessed using Pearson correlations and Bland-Altman analysis. Thereafter, a population-derived formula was developed and validated in a testing cohort.
resultsIn the 4-year training cohort (n = 81), the Original WTZ equation had the smallest mean difference of all equations. A higher mean difference [-0.362 mcg/mL (95% CI -0.585 to -0.138) vs. -0.054 mcg/mL (95% CI -0.186 to 0.078)] was observed in intensive care unit (ICU) patients compared with non-ICU patients. A cross-validated multivariable model improved the accuracy of free phenytoin estimation in ICU and non-ICU patients, even in the separate testing cohort (n = 52) with respective mean differences of -0.322 mcg/mL (95% CI -0.545 to -0.098) and -0.025 mcg/mL (95% CI -0.379 to 0.329) and was superior to the Original WTZ [mean difference -0.858 mcg/mL (95% CI -1.069 to -0.647) vs. -0.106 mcg/mL (95% CI -0.362 to 0.151), respectively].
conclusionsFree phenytoin levels in hospitalized patients cannot be accurately determined using available estimation equations, particularly in critically ill patients. Combining ICU status and other available clinical data can improve therapeutic drug monitoring and prevent high-magnitude errors, particularly when free phenytoin assays are not readily available.
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