Fig. 2.

Pharmacokinetics of ICIs. After intravenous administration, ICIs are distributed and metabolized by various routes. Extensive binding to target antigens in the (a) plasma or on (c) tissues, reduces the amount of free ICIs and increases the volume of distribution. (b) Transvascular movement of unbound ICIs is principally governed by means of convection, the magnitude of which is limited by factors such as organ perfusion and endothelial permeability. Within tissues, ICIs become distributed by means of diffusion and convection. (d) The FcRn is responsible for the transport of ICIs back into the vascular system, preventing the intracellular degradation of these drugs and hence prolonging their half-life. (e) On the other hand, the generation of antibodies against ICIs increases clearance. (f) However, the dominant mechanism of ICI clearance remains through proteolytic catabolism, which occurs in both plasma and peripheral tissues. (g) Lastly, the high-affinity interaction between ICIs and surface receptors precipitates an additional clearance route, i.e. that of receptor-mediated endocytosis. ADAs antidrug antibodies, ICIs immune checkpoint inhibitors, FcRn neonatal Fc receptor