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 (C_ss) 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-C_ss1) and solves for (a) maximum metabolic rate constant (V_max) assuming the population mean for the Michaelis constant (K_m) (method 1), and (b) K_m assuming the population mean for V_max (method 2). The derived estimates of V_max and K_m 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 C_ss error within 5 μg/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.