Projecting human pharmacokinetics of monoclonal antibodies from nonclinical data: comparative evaluation of prediction approaches in early drug development
Abstract
Currently, more than 350 monoclonal antibodies (mAbs) and mAb derivatives are under development as therapeutics. The prediction of mAb pharmacokinetics (PK)/pharmacodynamics (PD) plays a key role in starting dose selection for first‐in‐human (FIH) studies. This article presents a brief overview of the biology and mechanisms of absorption, distribution, metabolism and excretion (ADME) for mAbs. In addition, a detailed review of mAb human PK/PD prediction from nonclinical data is provided, including allometry for mAbs with linear or nonlinear PK, species‐invariant time method, physiologically based PK (PBPK) modeling and target‐mediated drug disposition (TMDD) model, bioavailability projection and immunogenicity impact on PK prediction. Finally, from an industry perspective a decision tree of mAb human PK projection is proposed to facilitate drug development. Copyright © 2015 John Wiley & Sons, Ltd.
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Two general approaches for antibodies with linear PK are commonly used to project mAb PK in humans.
“two general approaches for antibodies with linear PK are commonly used.”
From Tutorial on monoclonal antibody pharmacokinetics and its considerations in early development (2018) · cites this paper as [63]
The practice of projecting mAb PK in humans is well established.
“The practice of projecting mAb PK in humans is well established,63, 64, 65, 66, 67”
From Tutorial on monoclonal antibody pharmacokinetics and its considerations in early development (2018) · cites this paper as [63]
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References 81 · Cited by 69
- Authors
- Wang, J., Iyer, S., Fielder, P. J., Davis, J. D., & Deng, R.
- Affiliations
- Tesaro (United States) (US)
- Genentech (US)
- Corresponding author
- Deng, Rong
- Venue
- Biopharmaceutics & Drug Disposition
- Publisher
- Wiley
- Published
- 2015-05-15
- Volume
- 37
- Issue
- 2
- Pages
- 51-65
- ISSN
- 0142-2782 (ISSN-L)
- 1099-081X
- OpenAlex
- W1516429191
- Cited by
- 69
- References
- 81
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 6 · 2023: 7 · 2022: 9 · 2021: 6 · 2020: 6 · 2019: 7 · 2018: 8 · 2017: 9 · 2016: 5 · 2015: 1
- FWCI
- 6.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biopharmaceutics & Drug Disposition (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Keywords
- monoclonal antibodies, human pharmacokinetics, pharmacodynamics, allometry, target-mediated drug disposition, immunogenicity, first-in-human dose selection, early drug development
- MeSH terms
- Animals, Antibodies, Monoclonal, Decision Trees, Drug Evaluation, Preclinical, Humans, Models, Biological
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