Figure 2.

Structure of the whole body PBPK. (A) The organs are connected with plasma flow rate (Qorg, black line) and lymph flow rate (Jorg, gray line). Abbreviations: lung-lu, lymph nodes -ln, heart-he, GI tract-gi, liver-li, spleen-sp, pancreas-pa, skeletal muscle-mu, skin-sk, bone-bo, brain-br, thymus-th, adipose-ad, other-ot, kidney-ki. The organ subcompartments are vascular (v), interstitial (i), intracellular (IC) and endosomal (e). (B) Filtration-diffusion-driven solute exchange between the vascular and interstitial spaces takes place through small and large pores according to the two-pore hypothesis. Macropinocytosis (k_up) delivers extracellular proteins to the endosomal space where FcRn-mediated recycling (k_rec) back into vascular or interstitial space and nonspecific degradation (k_deg) take place. Organ-specific modifications are shown on Supplementary Figure 2