Systematic approach to a dosage regimen for phenytoin based on one-point, steady-state plasma concentration

A systematic approach to individualizing the phenytoin (PHT) dose from a previous dose (D) and steady-state concentration (Css) pair was established by the combined use of two methods based on recently reported population pharmacokinetic parameters. This system applies the Michaelis-Menten equation to the initial data pair (D1-Css1) and solves for (a) maximum metabolic rate constant (Vmax) assuming the population mean for the Michaelis constant (Km) (method 1), and (b) Km assuming the population mean for Vmax (method 2). The derived estimates of Vmax and Km are then put through a series of filters, which results in the selection of method 1 and/or method 2 or allocation of a third category that needs further evaluation. A simulation study was performed to find a series of filters. The presented approach was applied retrospectively to the patients' data of 35 sets. Accurate predictions of the Css error within 5 micrograms/ml were obtained in 84% of the 25 cases, and in 30% of the 10 cases excluded. This systematic approach gives better prediction performance in mean error, mean absolute error, and root mean square error than a Bayesian feedback method.