Unknown Dosing Histories

I would like to 'support' Rene Braekman's suggestion of including an 'unknown' C0 in the model and getting a pre-study day dose blood sample. I've used this approach with more traditional PK modeling (ie non-NONMEM :-)) and it works. It doesn't even have to be at steady state - just post absorption (and post-distribution if two compartment). If two compartment - post-distribution you can derive Ct(0) [zero time tissue compartment concentration from Cp(0) and k12, k21] so it isn't another adjustable parameter.