Development of the convenient and direct numerical analytical method of the pharmacokinetics of phenytoin by an ordinary and/or the Bayesian weighted least-squares method using the program MULTI2(BAYES).

A Simple and convenient numerical integration method was developed for the purpose of analyzing the pharmacokinetics of phenytoin not only at steady state but also at non-steady state. The algorithm was linked on a nonlinear least-squares method program MULTI2(BAYES). The computing time was significantly decreased compared to Runge-Kutta-Gill Method at analysis by the Simplex algorithm and calculating precision was higher, especially at a large integration interval. This method was found to be sufficiently applicable to the analyses of the serum concentrations of phenytoin at non-steady state as well as at steady state and the dosage adjustment by simulation. The flexibility of analyzed parameters on a microcomputer can be overcome by analyzing at the integration subinterval smaller than 0.25 h with the appropriate initial values of parameters, although very time consuming, or by using the Bayesian method with appropriate population parameters.