COMPARISON OF METHODS FOR THE PREDICTION OF PHENYTOIN CONCENTRATIONS

Summary A comparison was made of different methods for the prediction of the serum concentrations of phenytoin (PHT) at steady-state with a view to determining which of them had the best predictive performance. The methods employed calculated the predicted concentrations based on a dose steady-state concentration pair. Two of the methods used involved solving the Michaelis-Menten equation, determination of a single parameter in each individual and maintaining the Km (Method A) or Vmax (Method B) values at a constant. Methods C and D were Bayesian techniques that used population parameters determined in a population studied by us (Method C) and parameters drawn from the literature (Method D). Calculation of bias and precision suggests that Method C is the most suitable of those studied, with a mean prediction error (ME) of 0·56 ± 2·16 mg/litre, a mean absolute error (MAE) of 1·76 ± 1·31 mg/litre and a root mean squared prediction error (RMSE) of 2·17 mg/litre. Method C was also the method that showed the lowest percentage of underestimation (5·26%) and overestimation (10·53%).