GastroPlus simulation software

The CAT model was further modified to include pH-dependent solubility, dis-solution/precipitation, absorption in the stomach or colon, first-pass metabolism in gut or liver, and degradation in the lumen. Physiological and biochemical factors such as changes in absorption surface area, transporter, and efflux protein densities have also been incorporated. This advanced version of CAT, called ACAT [176], has been formulated in a commercially available simulation software product under the trademark name GastroPlus . A set of differential equations, which is solved by numerical integration, is used to describe the various drug processes of ACAT as depicted in Figure 6.4. 

As one part of our software validation, we tested the accuracy of GastroPlus simulation of fraction absorbed. Starting from two-dimensional structures, ADMET Predictor was used to generate the molecular descriptors and estimates of log P,... 

There have been considerable efforts toward modeling ADME/Tox properties and the biophysical properties of molecules (see chapters 18-20, 22, 28), including numerous commercial software solutions. Simulations Plus (http //www.simulations-plus.com/) have developed GastroPlus, a product... 

II. Product Summaries Simulations Plus develops simulation and predictive modeling software for in silico compound screening and for preclinical and clinical drug development in the area of Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET). The available applications include GastroPlus, ADMET Predictor, ADMET Modeler, DDDPlus, and MembranePlus. 

More recent PBPK software packages such as SIMCYP [www.simcyp.com], PK-Sim [www.pk-sim.com], GastroPlus [www.simulations-plus.com], and Cloe PK [www.cyprotex.com] offer similar bioavailability estimation. It is clear that these approaches require more data input than just molecular structure as in QSAR models. 

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