Evaluation of Single-Point Phenytoin Dosage Prediction Methods in Pediatric Patients

Abstract

Phenytoin (PHT) dosage adjustment in a clinical situation is difficult because of the nonlinear metabolism of the drug. Therefore, many techniques have been advocated to aid in dosage adjustments based on single-point PHT concentration determined at steady-state (SS). We retrospectively investigated seven methods in a population of 90 outpatients treated with PHT. The dose needed to achieve a desired PHT concentration at SS was calculated based on an observed SS dose-concentration pair using the Richens and Dunlop nomogram (RD), the Rambeck nomogram, the Martin nomogram, the Chiba nomogram, a population clearance method, the Wagner dosing equation and the Bayesian feedback method (B). Mean prediction error, mean absolute error (MAE), and root mean squared error (RMSE) were separately calculated for each method, and served as a measure of prediction bias and precision. The MAE and RMSE were lowest for method B (MAE=28.7 mg/d, RMSE=36.8 mg/d), followed by method RD (MAE=30.3 mg/d, RMSE=40.8 mg/d). Therefore, we recommend the use of method B to make routine PHT dosage adjustments in pediatric patients when only one dose and one concentration are available.