Application of Pharmacokinetic/Pharmacodynamic Modeling in the Development of Antibody-Based Therapeutics

Chapter

Abstract

Mathematical modeling of the time-course of drug exposure (pharmacokinetics, PK) and associated pharmacological effects (pharmacodynamics, PD) has evolved from a simple descriptive endeavor to an essential component of model-based drug development. The role of PK/PD modeling can be more critical for antibody-based therapeutics owing to their complex pharmacological properties. Nonlinear behavior can manifest in most of the physiological processes controlling antibody PK, and mechanisms of drug response are inherently nonlinear and often involve turnover of endogenous ligands and biomarkers. In this chapter, model concepts and features that are common to antibody-based therapeutics are highlighted, along with applications of such models for understanding inter-species differences in concentration-effect relationships, selecting first-in-human doses, designing regimens for clinical studies, and linking PK/PD relationships to clinical outcomes. To improve prospective model predictions of drug efficacy and safety, new approaches will be needed to link antibody disposition with robust systems pharmacology models of drug and disease mechanisms.

Keywords

Placebo Arthritis Convection Psoriasis Macromolecule 

Notes

Acknowledgments

Financial support from NIH Grant GM57980, the Center for Protein Therapeutics, University at Buffalo, SUNY (UB), and the UB-Pfizer Strategic Alliance is gratefully appreciated. I thank Dr. Sihem Ait-Oudhia at UB for her assistance in constructing figures.

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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  1. 1.Department of Pharmaceutical SciencesUniversity at Buffalo, State University of New YorkBuffaloUSA

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