Predicting unbound phenytoin concentrations in the critically ill neurosurgical patient

Ann Pharmacother. 1996 Mar;30(3):219-23. doi: 10.1177/106002809603000301.


Objective: To assess the correlation of measured unbound phenytoin concentration (dphF) to estimated unbound concentration (dphEF) using the Sheiner-Tozer equation in critically ill patients in the neurosurgical intensive care unit.

Design: The dphF and total phenytoin (dphT) trough serum concentrations were measured during the first week of therapy in 17 consecutive patients with albumin concentrations less than 3.5 g/dL. Serum albumin concentrations were measured within 24 hours of serum phenytoin concentration measurement.

Setting: A university-affiliated urban teaching hospital.

Participants: The study population consisted of 17 neurosurgical patients who were at least 18 years old.

Main outcome measures: The predictability of the Sheiner-Tozer equation was tested by measuring dphF, dphT, and serum albumin concentrations. Measured phenytoin concentrations were compared with phenytoin concentrations calculated from the Sheiner-Tozer equation. To estimate correlation between variables linear regression was calculated. Mean absolute value of error and mean error were estimated to assess precision and bias between measures, respectively.

Result: The mean +/- SD dphT was 13.05 +/- 5.15 mu g/mL. The measured dphF was 1.89 +/- 0.80 compared with 2.00 +/- 0.8 mu g/mL for the dphEF (NS). Regression analysis for dphEF versus dphF revealed a significant correlation (r2 = 0.94, p = 0.001). The mean absolute value of error for the Sheiner-Tozer equation to predict dphEF was 0.167, which was 9% of the mean value of dphEF (1.89).

Conclusions: These results indicate that, in this population, the Sheiner-Tozer estimate of dphEF provides an unbiased, precise clinical estimate of dphF in patients for whom measured dphF is unavailable or impractical.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Critical Illness*
  • Female
  • Humans
  • Intensive Care Units
  • Male
  • Mathematics
  • Middle Aged
  • Neurosurgery
  • Phenytoin / blood*
  • Phenytoin / pharmacokinetics
  • Postoperative Period
  • Serum Albumin / analysis*


  • Serum Albumin
  • Phenytoin