title: Application of pharmacokinetics-pharmacodynamics/clinical response modeling and simulation for biologics drug development.
abstract: 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.
authors.affiliation: Office of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA. liang.zhao@fda.hhs.gov
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.forename: Elizabeth Y
authors.initials: EY
authors.lastname: Shang
authors.forename: Chandrahas G
authors.initials: CG
authors.lastname: Sahajwalla
mesh_terms: D000818:Animals; D001688:Biological Products / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D003198:Computer Simulation; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D015201:Meta-Analysis as Topic; D008954:Models, Biological
chemical_list: D001688:Biological Products