Clinical utility of a new and simple technique for individualizing phenytoin dosage.

Abstract

Wagner proposed a new and simple method to predict dosage of drugs obeying simple Michaelis-Menten elimination kinetics. From his theory the following equation, Dn = Do + 1n (Cd/Co)/S can be derived, which forms the basis of predicting the required dosage (Dn) to obtain a desired steady-state concentration (Cd), using initial steady-state concentration (Co), obtained with initial dose (Do) and a population value of S for the drug. We retrospectively investigated the value of S for phenytoin (PHT) in a population of 55 outpatients who had three or more reliable measurements of the steady-state concentration of PHT in serum, measured while they were taking different daily doses. The value of S for PHT was estimated to be 0.0122759 in Japanese patients. The predictive performance of this equation was compared with Bayesian feedback method (B) using retrospective data from 220 outpatients. This equation yielded mean error (ME) of 0.0, mean absolute error (MAE) of 30.7 and root mean squared error (RMSE) of 40.9 mg/d compared to ME of -2.5, MAE of 30.3 and RMSE of 40.1 mg/d for B method. These results indicate that this equation may be a useful adjunct for prediction of PHT dosage as well as B method. Moreover, the simplicity of the equation allows calculation on a hand-held calculator.