I have a question related with the Enterohepatic Recycling (PML School Lesson 7), I have a model with OCA and its two metabolites which both have EHC. I used normal model (nonEHC) and EHC in different format (simply EHC and EHC with bile/gut compartments). However, the fitting always gives negative values though in the structure they all suppose to be positive (exp sturcture). I tried to give 0 limit but other parameter will turn to negative instead.
I have attached the file Test drug_test sample.phxproj 3.84MB 53 downloads. Apologies it may look over parameterized. The model is also referenced from the FDA review model and I have scale down the dataset with only five typical subjects so it won't take a long time to finish the fitting but the problems stay in a similar way. I would like to figure out why the parameter is negative and how can I improve it. The FDA example OCA POPPK model.pdf 588.45KB 54 downloads is also attached.