@sai_matcha I saw your question in NMUsers. Let me help you here.
0. It was not clear what the purpose of the modeling is.
- With oral parent dosing and having parent and metab PK - there is no way to estimate fpm. It will be same challenge for metab2.
- Think about this way - with only oral dosing - let us assume 1cmt model, we have 3 parameters F, ka, CL and V. With only oral dosing, you cannot estimate F (absolute bioavailability). Hence we estimate ka, CL/F and V/F.
- Similarly for metabolite, we do not know the fpm (fraction metabolized) from parent from this oral dosing study alone. You need the mass balance study - to know fm. Your parent-metab model will have fpm, CLpm, CLm and Vcm parameters. You cannot estimate all these parameters only with oral parent dosing. Hence you can fix fpm from the mass balance study. If the MW of metabolite is close to parent, you can try to fix the Vcm to Vcparent.
- the formula you quoted in your second response in NMusers estimated fpm as AUCm/AUCp. Please note this formula does not account for F (absolute bioavailability) of the parent. You gotto have the mass balance study.