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Comparison of two methods in the estimation of the pharmacokinetic parameters of phenytoin
D Santos Buelga1, A Vazquez, A C Alonso
1Department of Pharmacy, School of Pharmacy, University of Salamanca, Spain.
Abstract:
This report compares two different methods of estimating the pharmaco-kinetic parameters of phenytoin (PHT) from steady-state serum concentration data obtained in clinical practice: the standard two-stage method (STS) and the extended least squares method (ELS). The study was carried out with the data from 27 compliant adult epileptic patients treated with PHT on a monotherapy regimen. Application of Akaike information criterion (AIC) points to a better estimation with the STS method (AIC = 268.05 for ELS; AIC = 114.13 for STS). This was confirmed by calculating the mean prediction error (mpe) and the standard deviation of EMP, which were 0.59 +/- 6.11 mg/l and -0.12 +/- 2.93 mg/l for ELS, and STS methods, respectively. Despite the well-known limitations of the STS method, a simulation study revealed that it can be successfully used when the patients to be included are selected with great care and when reliable serum concentration data are available.
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