PK analysis of data from different occasions

Dear nmusers, I'm working on an PK analysis of a data set in NONMEM and have run into some questions. I would really appreciate if any of you have the chance to give me some suggestions. The data set I'm analyzing consist of concentration-time profiles obtained at three different occasions for every subject (n=20). Non-compartmental analysis and individual modeling indicate changes in CL/F between the occasions, possibly explained by renal function. If I analyze the occasions separately, a two-compartment model describes the data well at occasions 2 and 3, but not at occasion 1. At occasion 1 large inter-individual variation is observed and a one-compartment model can to some degree describe the data. If I analyze all occasions simultaneously with between-occasion variation, a one-compartment model is able to fit the data reasonably well (two-compartment model is not considered robust). The parameter estimates are in the right ball park, but GOF plots from the simultaneous analysis indicate model misspecification typical for a one-compartment model fit of "two-compartment data". My question is therefore how I should proceed? Will separate or simultaneous modeling be most ideal and what should I consider to get most relevant information? Best regards, Havard Havard Thogersen, Master student University of Oslo/Cincinnati Children's Hospital Medical Center Pediatric Pharmacology Research Unit and Laboratory of Applied Pharmacokinetics & TDM Cincinnati Children's Hospital Medical Center 3333 Burnet Avenue, MLC 6018 Cincinnati, OH 45229-3039 Phone: (513) 636-9011