Characterization of Free Phenytoin Concentrations in End-Stage Renal Disease Using the Winter-Tozer Equation

Ann Pharmacother. 2017 Aug;51(8):669-674. doi: 10.1177/1060028017707541. Epub 2017 May 4.


Background: The Winter-Tozer (WT) equation has been shown to reliably predict free phenytoin levels in healthy patients. In patients with end-stage renal disease (ESRD), phenytoin-albumin binding is altered and, thus, affects interpretation of total serum levels. Although an ESRD WT equation was historically proposed for this population, there is a lack of data evaluating its accuracy.

Objective: The objective of this study was to determine the accuracy of the ESRD WT equation in predicting free serum phenytoin concentration in patients with ESRD on hemodialysis (HD).

Methods: A retrospective analysis of adult patients with ESRD on HD and concurrent free and total phenytoin concentrations was conducted. Each patient's true free phenytoin concentration was compared with a calculated value using the ESRD WT equation and a revised version of the ESRD WT equation.

Results: A total of 21 patients were included for analysis. The ESRD WT equation produced a percentage error of 75% and a root mean square error of 1.76 µg/mL. Additionally, 67% of the samples had an error >50% when using the ESRD WT equation. A revised equation was found to have high predictive accuracy, with only 5% of the samples demonstrating >50% error.

Conclusion: The ESRD WT equation was not accurate in predicting free phenytoin concentration in patients with ESRD on HD. A revised ESRD WT equation was found to be significantly more accurate. Given the small study sample, further studies are required to fully evaluate the clinical utility of the revised ESRD WT equation.

Keywords: anticonvulsants; end-stage renal disease; epilepsy; pharmacokinetics; phenytoin; therapeutic monitoring.

MeSH terms

  • Adult
  • Albumins / metabolism
  • Anticonvulsants / blood*
  • Anticonvulsants / therapeutic use
  • Female
  • Humans
  • Kidney Failure, Chronic / blood*
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / therapy
  • Male
  • Middle Aged
  • Models, Biological*
  • Phenytoin / administration & dosage
  • Phenytoin / blood*
  • Phenytoin / therapeutic use
  • Protein Binding
  • Renal Dialysis*
  • Retrospective Studies


  • Albumins
  • Anticonvulsants
  • Phenytoin