Phenytoin Dosage Predictions in Paediatric Patients

SummaryPhenytoin dosing in paediatric patients is complicated both by alterations in patient requirements due to growth and maturation changes and by the capacity-limited characteristics of Phenytoin metabolism. This study examines 2 pharmacokinetic methods to adjust Phenytoin dosage based on a single dosing-rate/steady-state serum Phenytoin concentration pair. A Bayesian forecaster and a fixed parameter [rate of metabolism (Vmax)] method were examined with previously published sets of a priori parameter estimates. The fixed Vmaxmethod was utilised with the parameter derived from native Japanese (method 1), US Caucasian (method 2) and European (method 3) patients. The Bayesian forecaster used a priori parameter estimates obtained from native Japanese (method 4) and European (method 5) patients. Each method was examined retrospectively in 34 paediatric patients with a total of 48 predictions possible. Measures of absolute predictability, bias (mean error, % dose) and precision (root mean squared error, % dose), were −3.58/12.2, −1.51/12.2, 4.06/9.96, −4.38/13.2, and −3.10/11.5, for methods 1, 2, 3, 4 and 5, respectively. There was no significant difference among the 5 methods. However, the Bayesian algorithm tended to be more robust over a broad range of situations, providing predictions in all cases. The fixed Vmaxmethods could not provide predictions in every case. Finally, all methods had a significant number of overpredictions of dosage. Poorer results were observed when prediction of steady-state serum concentrations were performed, partly due to the retrospective nature of the study. We conclude that close monitoring of patients, regardless of the method chosen to adjust dosage, is recommended.