Figure 1.

Schematic of the whole-body PBPK model for mAbs following IV administration. (a) overall circulatory model. (b) Organ-level structure of a typical tissue, including vascular space, endothelial space, interstitial space, and cell space. Paracellular transport via convection and diffusion through pores is depicted along with endothelial transport and process. (c) Endosomal subcompartments, showing the competition between endogenous IgG and mAb for FcRn at a specific pH value.

Long Description: Whole-body PBPK model diagrams. (a) An overall flow diagram with separate boxes representing different organs (such as lung, heart, liver), central venous plasma, central arterial plasma, lymph node, and lymphatic vessels. They are connected using solid lines via plasma flows and lymph flows anatomically. An arrow into central venous plasma labels an intravenous dose. In addition, dashed arrows drawn from muscle and skin point to a peripheral sampling site. (b) A box is divided into different spaces labeled as vascular space, endothelial space, interstitial space, cell space from top to bottom. Arrows labeled with Q and Q-L flow into and out of vascular space, respectively. Two solid flow arrows labeled with convection move from vascular space to interstitial space through a large pore and a small pore between endothelial space. Besides each of them is a dashed flow arrow labeled as diffusion, moving bi-directionally between vascular and interstitial spaces. Within endothelial space, three ellipses indicated as “Early pH 7.4a,” “Late pH 6.0,” and “Recycling pH 7.4b” are connected sequentially from left to right, with a recycling arrow from the last ellipse to the first one and an elimination arrow from the second ellipse. There are two arrows labeled as S_pino·CL_pino into the first ellipse from vascular space and interstitial space, respectively. From the last ellipse there are two arrows flowing into vascular space and interstitial space. Lastly, a flow termed as L moves out of interstitial space. (c) A zoomed ellipse of endothelial endosomal space. On the top within the ellipse, there are FcRn, plus sign, IgG on the left side of bi-directional arrows and IgG-FcRn on the right side. The arrow going from left to right is labeled with k_on^pHx and the reverse arrow labeled with k_off^pHx. On the bottom within the ellipse, there is same arrangement with FcRn, mAb, and mAb-FcRn.