Target‐Driven Pharmacokinetics of Biotherapeutics

Abstract

Abstract Target‐driven pharmacokinetic (PK) is a peculiar characteristic of therapeutic monoclonal antibodies (mAbs). Target‐mediated drug disposition (TMDD) includes the processes of binding of the mAb to its antigen and elimination of the mAb‐antigen complex. This chapter reviews different modeling approaches that can be used to analyze, simulate, and infer target‐driven PK of mAbs: the classical (whole‐body) TMDD modeling approach, including its various approximations (such as the Michaelis‐Menten approximation), the cell‐level TMDD modeling approach, and the simplified physiologically‐based pharmacokinetic (PBPK) modeling approach. It discusses the classical whole‐body TMDD model and the characteristic features of TMDD profiles, and reviews various reduced TMDD models and their underlying assumptions. Cell‐level TMDD and simplified PBPK models are also reviewed as two approaches that allow to integrate prior information on the targeted system and the species physiology into the modeling process.