Why should we avoid using micro rate constants?

Hello everyone! I have a question. I was trying to build a 2-compartment PK model for marijuana use in occasional and chronic smokers. Initially, I was using providing rate constants K12 and K21 in PK block and it resulted in poor fitting. Then, I later changed to CL,V1, V2 , Q and it resulted in proper fitting. I was perplexed as to why I couldn't get a proper fit by providing rate constants? I tried to look online but couldn't find any proper explanation about when (or not) we should use micro constants in PK block to define our model in NONMEM? Does anyone has any useful insights into this? Regards, Sumeet Singla Graduate Student Dpt. of Pharmaceutics & Translational Therapeutics College of Pharmacy- University of Iowa