• Liang Zhao, Elizabeth Y Shang, and Chandrahas G Sahajwalla.
• Office of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA. liang.zhao@fda.hhs.gov
• J Pharm Sci. 2012 Dec 1; 101 (12): 4367-82.

AbstractBiologics, 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.Copyright © 2012 Wiley Periodicals, Inc.

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