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U.S. Department of Health and Human Services

Scientific Publications by FDA Staff

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J Pharm Sci 2012 Dec;101(12):4367-82

Application of pharmacokinetics-pharmacodynamics/clinical response modeling and simulation for biologics drug development.

Zhao L, Shang EY, Sahajwalla CG


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.

Category: Journal Article, Review
PubMed ID: #23018763 DOI: 10.1002/jps.23330
Includes FDA Authors from Scientific Area(s): Drugs
Entry Created: 2012-09-29 Entry Last Modified: 2016-03-21