Laboratoire de Pharmacologie, Faculte de Medecine, Creteil, France
This project is developed for population pharmacokinetic modeling of experimental data. The program is written in Pascal language based on the high-level Windows graphical interface. This provides a user-friendly tool that allows easy and fast modelisation of the data; different combinations of covariates can be ascribed to one or several pharmacokinetic parameters; the individual time-courses can be grouped according to a scalar covariate with the estimation of specific group parameter(s). The population pharmacokinetic parameters, the inter-individual variabilities around these parameters and the intra-individual variability for the time-courses are estimated by the minimization of the extended least-squares (ELS) criterion via the use of Simplex, Powell, BFGS or Polak-Ribiere algorithms. Several statistical models are available for intra- and inter-individual variations, homoscedastic, proportional or multiplicative error model. For each analysis, the program outputs the ELS function, the Akaike's information criterion (for rapid comparison between models), the parameters and variabilities estimated, the listing of all time-courses with observed and calculated dependent variables. Graphical representations are immediately available, kinetic plots, residual plots and residual versus covariate plots. A number of tool commands allow to get covariates statistics, mean and individual pharmacokinetic parameters according to covariate values, and non compartmental and compartmental mean parameters. The importation of NM-TRAN formatted files is possible.