Development of a compartmental model of human zinc metabolism: identifiability and multiple studies analyses

A compartmental model of zinc metabolism has been developed from stable iso tope tracer studies of five healthy adults. Multiple isotope tracers were a dministered orally and intravenously, and the resulting enrichment was meas ured in plasma, erythrocytes, urine, and feces for as long as 3 wk. Data fr om total zinc measurements and model-independent calculations of various st eady-state parameters were also modeled with the kinetic data. A structure comprised of 14 compartments and as many as 25 unknown kinetic parameters w as developed to adequately model the data from each of the individual studi es. The structural identifiability of the model was established using the G LOBI2 identifiability analysis software. Numerical identifiability of param eter estimates was evaluated using statistical data provided by SAAM. A maj ority of the model parameters was estimated with sufficient statistical cer tainty to be considered well determined. After the fitting of the model and data from the individual studies using SAAM/CONSAM, results were submitted to SAAM extended multiple studies analysis for aggregation into a single s et of population parameters and statistics. The model was judged to be vali d based on criteria described elsewhere.