Phenytoin dosage individualization--five methods compared in the elderly

Five methods to predict phenytoin dosage have been compared in nine continuous care elderly patients. For each patient three steady-state plasma concentrations were obtained at three different doses. The data were used to estimate the 'optimum' dose for each patient by direct linear plot. The optimum dose for each patient was predicted from each plasma concentration using five dosage prediction methods based on the Michaelis-Menten equation using: (i) the population mean Vmax, (ii) the population mean KM, (iii) the linearized Bayesian method, (iv) the Rambeck nomogram, and (v) two plasma concentration-dose data pairs to estimate both Vmax and KM. The predictive precision was similar for each of methods (i-iv). Ninety-six out of 126 dosage predictions with the five methods were within 25 mg of the optimum dose. Methods (ii) and (iv) tended to overpredict dosage, particularly when used to interpret low plasma phenytoin concentrations.