The predictive performances of equations used to estimate unbound phenytoin concentrations in a medical ICU population and the impact of exogenous albumin administration☆

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Abstract

Purpose:

This study evaluated the predictive performances of four equations (Sheiner-Tozer [ST], Kane-modified ST, Anderson-modified ST, and Cheng-modified ST) used to estimate free phenytoin concentrations in a medical intensive care unit (MICU) and assessed the impact of exogenously administered albumin.

Methods:

Thirty MICU subjects receiving phenytoin were retrospectively evaluated. Predictive performances were assessed by mean absolute error (MAE), mean prediction error (MPE), and root mean squared error (RMSE); linear regression of predicted vs. actual unbound concentrations; and Bland-Altman plots. Parameters were further delineated by recent exogenous albumin administration.

Results:

The measured unbound phenytoin concentration was 2.14 ± 0.84 μg/mL for all 90 levels, 1.89 ± 0.92 μg/mL for the 58 levels without albumin, and 2.58 ± 0.83 μg/mL (p < 0.0001 vs. without albumin) for the 32 levels after exogenous albumin. R2 values were below 0.4 for all equations. The ST equation over-predicted unbound concentrations whereas all other equations under-estimated unbound concentrations. All equations possessed bias and lacked precision. Bland-Altman plots demonstrated greatest bias with the ST equation. Albumin administration introduced additional bias, limited precision, reduced R2 values, and completely negated the performances of the ST and Kane-modified ST equations.

Conclusion:

Estimating unbound concentrations with equations in the MICU population is discouraged.

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