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%).
Vázquez Rodríguez
A
A
Department of Pharmacy, School of Pharmacy, University of Salamanca, Spain.
Santos Buelga
D
D
Alonso González
A C
AC
Garcćia Sánchez
M J
MJ
Domínguez-Gil Hurlé
A
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001499:Bayes Theorem; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D016013:Likelihood Functions; D008875:Middle Aged; D010672:Phenytoin / Q000008:administration & dosage / Q000097:blood*; D012044:Regression Analysis
D010672:Phenytoin