Fig. 6.

Simulated profiles of antibody PK, target receptor occupancy and displaced ligand in humans following a single 100 mg IV administration of an antibody directed against a cell surface target receptor. Fast- and slow-internalization rates correspond to receptor internalization T ½ of 30 min and 2 h, respectively. The presumed affinity of the endogenous ligand to receptor is 0.01 nM. Symbols represent the antibody affinity (Kd = 0.1, 0.3 or 1 nM). R₀ is the expression level of the receptor at baseline. As shown in these graphs, target receptor expression level and internalization rate are two primary determinants of in vivo antibody PK, target receptor occupancy, and displaced ligand profiles.