Fixed Dosing versus Body‐Size‐Based Dosing for Therapeutic Biologics—A Clinical Pharmacology Strategy

This chapter focuses on the dosing strategies for therapeutic biologics in human adult populations, and it is acknowledged that the strategies for the dosing of pediatric populations may be different. The aim of any dosing strategy for a therapeutic agent is to optimize the overall clinical performance within an intended indication by maximizing the efficacious effect while minimizing the adverse events within the target patient population. The performance of body-size-based dosing and fixed-dosing approaches have been evaluated for monoclonal antibodies (mAbs) and therapeutic peptides/proteins, in terms of their population and individual performances in reducing intersubject pharmacokinetic (PK) and/or pharmacodynamic (PD) variability in adult patients. The results of these simulation studies have demonstrated that in contrast to conventional assumption, body-size-based dosing did not always result in less intersubject variability in drug exposure and PD measurements when compared to fixed-dosing approaches. Keywords: body-size-based dosing; fixed-dosing approaches; monoclonal antibodies; pharmacodynamic variability; pharmacokinetic variability; therapeutic biologics