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Comparison of methods for the prediction of phenytoin concentrations.

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%).