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)

概要

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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 nonsteady 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.
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