Andreas Steingoetter1, Dieter Menne2, Rickmer Braren3
1Division of Gastroenterology & Hepatology, University Zurich, Zurich, Switzerland; 2Menne Biomed Consulting, Tuebingen, Germany; 3Institute of Radiology, Klinikum rechts der Isar der TU Mnchen, Munich, Germany
Integration of several individual tissue concentration curves within a study population could allow for the development of complex multiple compartment models. Based on population nonlinear mixed effects (popPK) modeling using NONMEM 7, this study aimed at developing and evaluating a robust multi-compartment popPK model for Gd-DTPA in a rat hepatocellular carcinoma (HCC). The final numerically stable model, consisting of 3 observed (muscle, tumor, liver) and 6 unobserved compartments, was validated using standard numerical criteria (i.e. weighted residuals, caterpillar plots, objective function value, standard errors, matrix condition number) and quantitative histological analysis (tumor necrosis).