PHARMACOKINETIC-PHARMACODYNAMIC AND METABOLITE MODELING WITH TOPFIT

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