Physiologically-based modeling of monoclonal antibody pharmacokinetics in drug discovery and development

Drug Metab Pharmacokinet. 2019 Feb;34(1):3-13. doi: 10.1016/j.dmpk.2018.11.002. Epub 2018 Nov 22.


Over the past few decades, monoclonal antibodies (mAbs) have become one of the most important and fastest growing classes of therapeutic molecules, with applications in a wide variety of disease areas. As such, understanding of the determinants of mAb pharmacokinetic (PK) processes (absorption, distribution, metabolism, and elimination) is crucial in developing safe and efficacious therapeutics. In the present review, we discuss the use of physiologically-based pharmacokinetic (PBPK) models as an approach to characterize the in vivo behavior of mAbs, in the context of the key PK processes that should be considered in these models. Additionally, we discuss current and potential future applications of PBPK in the drug discovery and development timeline for mAbs, spanning from identification of potential target molecules to prediction of potential drug-drug interactions. Finally, we conclude with a discussion of currently available PBPK models for mAbs that could be implemented in the drug development process.

Keywords: Drug development; Drug discovery; Monoclonal antibodies; Pharmacokinetics; Physiologically-based pharmacokinetics.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / pharmacokinetics*
  • Drug Development / methods
  • Drug Development / trends*
  • Drug Discovery / methods
  • Drug Discovery / trends*
  • Humans
  • Models, Biological*
  • Tissue Distribution / drug effects
  • Tissue Distribution / physiology


  • Antibodies, Monoclonal