Physiologically based pharmacokinetic models are tools for better understanding and prediction of effects of drugs on the body. In this thesis we have developed a methodology of bioequivalence study simulations with commercially available program GastroPlusTM. Firstly we have studied the literature and previously described methodology for bioequivalence studies and on the basis of already described challenges developed our own method of bioequivalence studies simulations. The advantage of the developed method is that includes inter- as well as intrasubject variability. It allows us to assess the probability of passing bioequivalence study when repeating a big enough number of simulations. The key challenge remains characterising key population parameters and right variability of those. Methodology was tested on model drug, acetylsalicylic acid. For the purpose of this research we have prepared seven hypothetical formulations with different dissolution profiles based on changing particle size. We have used three different stomach transit times t = 0.10, 0.25 in 0.5 h and evaluate the effect of different transit times on plasma concentrations. Furthermore, we have also evaluated the effect of number of people in the sample and added intrasubject variability. The program allows us to perform crossover studies, as we can use the same population to conduct virtual study on different formulations. Therefore, we used same population and ran virtual simulation on 1000 subjects for all seven formulations in interval of four hours and 62 sample points. The developed methodology can be widely used for other substances and formulations, and is a new useful tool in designing bioequivalence studies. Computer simulations using physiologically based pharmacokinetic models are tools in drug development that help us predict the success of bioequivalence studies, allow cheaper and faster drug development and consequently, better access to new pharmaceutical products.
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