Quantitative Pharmacology and Individualized Therapy Strategies in Development of Therapeutic Proteins for Immune-Mediated Inflammatory Diseases

12Pharmacokinetics‐Based Dosing Strategies for Therapeutic Proteins in Inflammatory Bowel Disease

Diane R. Mould¹Richard N. Upton² and Jessica Wojciechowski³

¹Projections Research Inc., Phoenixville, PA, USA

²University of South Australia, School of Pharmacy and Medical Sciences, Adelaide, SA, Australia

³Pfizer Inc., Groton, CT, USA

12.1 Introduction

The pharmacokinetics (PK) of monoclonal antibodies (mAbs) exhibit substantial differences from that of chemical agents. The clearance (CL) mechanisms for mAbs differ from routes commonly reported for chemical therapeutics, and the effects of demographic characteristics, patient characteristics, and concomitant medications on the pharmacokinetic behavior of such agents may be quite distinct. Furthermore, the pharmacodynamics (PD) of mAbs often impact pharmacokinetic behavior, resulting in complex pharmacokinetic and pharmacodynamic behavior. Consequently, it is important to understand the unique characteristics of mAb pharmacokinetics as well as the pharmacology of the agent and aspects of the therapeutic area to optimally utilize therapeutic mAbs [1].

The first mAb (Orthoclone, OKT3) was approved for use in the treatment of acute rejection for renal transplant in 1986. Since that time, the number of mAbs in development and on the market has grown, and the class has expanded to cover antibodies, antibody fragments, antibody‐fusion proteins, antibody‐drug conjugates, and other forms. As a murine mAb, OKT3 taught a lot about anti‐drug ...