One‐point Feedback Control Method for Phenytoin Dosage Adjustment

Abstract— Routine clinical pharmacokinetic data collected from patients receiving phenytoin have been analysed to propose a new and simple equation to aid the dosage adjustment of this drug. The data were analysed using NONMEM, a computer program designed for population pharmacokinetic analysis that allows pooling of data. The rate equation for the elimination of phenytoin can be written as Do = kCssn, which fits the steady‐state serum concentration (Css) and daily dose data (Do). The parameter n is the kinetic order and the parameter k is an arbitrary rate constant. From the above equation, D2 = D1C1 −nC2n can be derived, which forms the basis of predicting the dosage, D2, to obtain a desired Css, Q2, using one initial Css, C1, obtained with an initial dose, D1 and using a population value of n. The value of n for phenytoin was estimated to be 0·312 in this study. The predictive performance of this equation was compared with the Richens and Dunlop nomogram and Bayesian feedback method using two or more steady‐state concentration/dose pairs from each of 78 outpatients. This equation allowed the prediction of a dose needed to produce a desired steady‐state concentration with errors comparable with the Bayesian feedback method for therapeutic drug monitoring.