6.6.3. Comparison with GastroPlus simulations
You may wish to compare results from an HTPK Simulation run in Predictor with the results from a simulation run in GastroPlus using the property predictions from ADMET Predictor. When you import structures into GastroPlus version 9.9, the default PK Model selection in the Import Structure Properties dialog is Compartmental and, assuming you have licensed the optional ADMET Predictor module, the clearance is set to be the predicted total liver microsome clearance from ADMET Predictor. You should leave both of these settings at their defaults.
GastroPlus by default uses ADMET Predictor's model for volume of distribution, so the simulation in ADMET Predictor must use the same setting. If you wish to use the mechanistic volume of distribution in ADMET Predictor, then that value must be exported to the structure file that you import into GastroPlus, because GastroPlus does not calculate this volume when performing compartmental simulations.
When running the ADMET Predictor simulation, you should turn on the option for using the adjusted fup, since GastroPlus uses this adjustment for computing the plasma clearance. The other ADMET Predictor setting you may wish to change is the flag for adding a renal component (fup*GFR) to the clearance calculation. GastroPlus does not add this renal term for compartmental simulations, so it is best to turn it off in Predictor if you plan to compare results with GastroPlus.
You can also choose to run a GastroPlus PBPK simulation. Note that ADMET Predictor's HTPK Simulation may be considered by some not to be a true PBPK simulation, since it lumps together all organs outside of the liver and digestive tract into a single Central compartment, whereas GastroPlus treats the flow through each organ separately. However, you can choose to run HTPK using the mechanistic volume of distribution rather than the statistical model. This makes comparison with PBPK possible, because the mechanistic volume of distribution is essentially a summation of the effective volumes calculated for the individual organs. To make a comparison using PBPK in human, you should change the GastroPlus PK Model physiology to HumanAmericanMale30YO_70kg before running any simulations; this will shift the volume of distribution to the mechanistic model. In ADMET Predictor, ensure that you have selected <Mechanistic> as the volume of distribution (Advanced dialog).