Pharmacokinetics/Pharmacodynamics and Disposition of Antibody-Drug Conjugates

摘要: Antibody-drug conjugates (ADCs) combine the high target specificity and favorable pharmacokinetics of monoclonal antibodies with potent tumor-killing properties cytotoxic agents, have demonstrated convincing antitumor effect in both animal models patients. However, inherent complexity ADCs their multiple components often makes development challenging. Pharmacokinetic absorption, distribution, metabolism, excretion (ADME) characterization reflects dynamic interactions between biological system ADC, provides critical assessments lead selection, optimization, clinical development. A rational strategy integrating mechanistic understanding pharmacokinetic/pharmacodynamics ADC disposition helps to inform drug linker design, ultimately maximize therapeutic window. In this chapter, we give an overview PKPD disposition, discuss our current major determinants, unique challenges, lessons learned from landscape. The utility pharmacokinetics–pharmacodynamics (PKPD) modeling is also discussed context providing guidance assist successful these complex molecules.