Absorption, distribution, metabolism, and excretion considerations for the development of antibody-drug conjugates

Abstract

Antibody-drug conjugates (ADCs) are a class of therapeutics that are designed to deliver potent small-molecule drugs selectively to cells that express a specific target antigen while limiting systemic exposure to the drug. This is accomplished by conjugating a potent drug onto an antibody-based therapeutic with a linker that is exquisitely stable in plasma. The development of an effective ADC requires optimizing a number of design elements and an extensive understanding of absorption, distribution, metabolism/catabolism, and elimination (ADME) processes for the ADC construct. Furthermore, as ADCs are a combination of an antibody and small-molecule drug, understanding key aspects of the ADME of each individual component is needed. This review aims to provide considerations for the development of ADCs from an ADME point of view.