Comparison of single-point phenytoin dosage prediction techniques

To dose the anticonvulsant phenytoin (PHT) in a clinical situation is difficult because of the non-linear metabolism of the drug. Therefore many techniques have been advocated to aid dosage adjustments based on a single-point PHT concentration determined at steady-state (ss). We retrospectively investigated six methods in a population of 130 out-patients 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 a Bayesian feedback method (B), the Richens and Dunlop nomogram (RD), the Rambeck nomogram (R), the Martin nomogram (M), a population clearance equation (PC), and the Wagner equation (W). The mean prediction error (ME), 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 MEs for B, RD, R, M, PC, and W, respectively, were -0.4, 1.2, 6.9, 3.4, -1.8, and 0.0 mg/day. The MAEs were 33.9, 38.5, 44.3, 50.4, 43.5, and 53.7 mg/day. The RMSEs were 43.7, 53.1, 65.2, 63.5, 56.0, and 68.2 mg/day. The MAE and RMSE showed lowest values for method B, followed by method RD. Therefore, we assume that method B is the most accurate in making routine PHT dosage adjustments.