In this review article, Zhao et al. discuss the guiding principle and the core mathematical modeling underlying PK or PK-PD model used.
Application of pharmacokinetics-pharmacodynamics/clinical response modeling and simulation for biologics drug development.
Zhao L, Shang EY, Sahajwalla CG.
J Pharm Sci. 2012 Dec;101(12):4367-82
Biologics, specifically monoclonal antibody (mAb) drugs, have unique pharmacokinetic (PK) and pharmacodynamic (PD) characteristics as opposed to small molecules. Under the paradigm of model-based drug development, PK-PD/clinical response models offer critical insight in guiding biologics development at various stages. On the basis of the molecular structure and corresponding properties of biologics, typical mechanism-based [target-mediated drug disposition (TMDD)], physiologically based PK, PK-PD, and dose-response meta-analysis models are summarized. Examples of using TMDD, PK-PD, and meta-analysis in helping starting dose determination in first-in-human studies and dosing regimen optimization in phase II/III trials are discussed. Instead of covering the entirety of model-based biologics development, this review focuses on the guiding principles and the core mathematical descriptions underlying the PK or PK-PD models most used.