Separation of the PK parameters for mixed endogenous and exogenous substances.

Dear NONMEM users, I encountered a case when an endogenous substance and an exogenous substance were not separated by any analytical method or using isotopes, which means we have a mix of both substances in the central compartment. 1. What are the possible methods to predict their pharmacokinetics? 2. Is it valid to use the clearance and volume of distribution of the total substance? 3. if I use the central compartment for the endogenous substance DADTendo (which contains the total) and create a dummy compartment for the exogenous substance DADTexo, would then be possible to account separately for each of their pharmacokinetics (CL, V) when we set the IPRED = A(endo) + A(exo)? Note: the endogenous substances are not in a steady state Regard Karam Alali PhD Candidate Clinical Pharmacy Discipline Universiti Sains Malaysia