Pharmacokinetic Models for FcRn-Mediated IgG Disposition

Figure 1

The proposed cutoff PK models. The full physiological model scheme (upper panel) describes physical processes, including IgG distribution in central, peripheral, and endosome compartments, nonspecific elimination from central compartment (CL), and FcRn-mediated endosomal IgG recycling and elimination in the endosome. The endosome space is nested in the peripheral compartment. In the reduced cutoff PK model scheme (lower panel), the endosome compartment is collapsed. The net endosomal IgG clearance is determined by endosomal uptake clearance (CL_𝑈) from the peripheral compartment, the FcRn capacity (Max), the total IgG concentration in peripheral compartment (𝐶_𝑃,𝑇), and the unbound fraction (𝑓_𝑈), where 𝑓_𝑈=(𝐶_𝑃,𝑇−Max)/𝐶_𝑃,𝑇 if 𝐶_𝑃,𝑇>Max; 𝑓_𝑈=0 if 𝐶_𝑃,𝑇<Max or in FcRn KO mice.