Fig 1.
Major components and processes of whole-body iron metabolism incorporated in the model.
Fig 2.
Key transport and reaction processes of iron metabolism involving four model compartments: Blood (B), reticuloendothelial system (RES), bone marrow (BM) and liver (L).
Four different types of arrows are used to connect compartments and species which are explained in the legend drawn inside the figure.
Table 1.
Reactions in blood (B) compartment.
Table 2.
Reactions in the erythroblast (EB) compartment.
Table 3.
Reactions in the RES (I, M, ISF) compartment.
Table 4.
Reaction terms in liver (L) compartment.
Table 5.
Steady-state relationships between parameters.
Table 6.
Parameter values obtained from literature.
Table 7.
Parameter values from literature different between human and mouse model.
Table 8.
Estimated parameters for pharmacokinetics and pharmacodynamics of rEpo.
Fig 3.
Comparison of model output (solid line) to experimental data (*) of relative changes in (A) hematocrit and (B) erythropoietin concentration in plasma for 60 days in response to phlebotomy.
Table 9.
Parameter values estimated based on experimental data.
Fig 4.
Comparison of model-simulated serum iron to experimental data in mouse after rhHepc injection (A) Time course after injection of 50 μg of rhHepc; solid line is the model output and (*) represent the experimental data (B) maximum change of serum iron with different doses of rhHepc.
Table 10.
Estimated parameter for mouse pharmacokinetics of rhHepc.
Fig 5.
Comparison of simulated (solid line) responses to iron ingestion to experimental data (*) for a short period of 2h past iron ingestion—(A) Serum iron (B) Transferrin saturation (C) Hepcidin concentration. The naturally damped oscillations produced as a result are shown by simulation of a longer time period (5 days) for the same variables (D-F).
Fig 6.
Model simulation to show the variation in (A) serum iron-hemoglobin (mg/dL), (B) serum iron (μg/dL), (C) intracellular ferroportin (FPN), (D) efflux of iron from RES (μmoles/min), when a CKD patient is treated with combination of epoietin-alpha (rEpo = 100 μg/Kg) and IV Iron Dextran (1g) every 2 weeks for 12 months. The time course of change of all four variables over time have been plotted from the start of the treatment at time 0.
Table 11.
Initial values of all species.