A program package for simulation and parameter estimation in pharmacokinetic systems.

A set of programs is presented which has been developed for parameter estimation and simulation of models arising from pharmacokinetic applications. The programs can accommodate linear and nonlinear models with multiple inputs and multiple outputs. When the model is defined by differential equations, non-uniform repetitive dosage regimens can be handled. The model may also be entered in integrated form when single dose studies or uniform multiple dose studies are being considered. The programs employ a variable-step, variable-order integration routine to solve the model differential equations, and the Nelder-Mead simplex procedure to determine the parameter values which minimize a weighted least squares criterion. The programs have been written for an interactive time-sharing environment with the experimental data and model equations stored in files for future use.