PHARMACOKINETIC-PHARMACODYNAMIC AND METABOLITE MODELING WITH TOPFIT

Two examples illustrating the ease of use and powerful data fitting and simulation techniques provided by the validated program TopFit 2.0 for the PC are presented. In the first, kinetics of parent compound and metabolite for (+) and (-) enantiomers of a racemic compound X were determined during a Phase III clinical study. Four data sets were fitted simultaneously for each patient. The model could be defined by the user without programming differential equations. The fit results indicated enantiomer specific kinetics for the metabolite but not for parent compound. In the second example, a model with nonlinear elimination and an E(max)-effect function was used to simultaneously fit data from six doses of compound Yin a Phase I study, The fitted parameters predicted the feasibility of a twice-daily dose regimen despite a very short plasma half-life of the compound. In conclusion, TopFit provides rapid and cost-effective support in analysis and design of clinical trials.