Physiochemical and Biochemical Factors Influencing the Pharmacokinetics of Antibody Therapeutics
Open accessAbstract
Monoclonal antibodies are increasingly being developed to treat multiple disease areas, including those related to oncology, immunology, neurology, and ophthalmology. There are multiple factors, such as charge, size, neonatal Fc receptor (FcRn) binding affinity, target affinity and biology, immunoglobulin G (IgG) subclass, degree and type of glycosylation, injection route, and injection site, that could affect the pharmacokinetics (PK) of these large macromolecular therapeutics, which in turn could have ramifications on their efficacy and safety. This minireview examines how characteristics of the antibodies could be altered to change their PK profiles. For example, it was observed that a net charge modification of at least a 1-unit shift in isoelectric point altered antibody clearance. Antibodies with enhanced affinity for FcRn at pH 6.0 display longer serum half-lives and slower clearances than wild type. Antibody fragments have different clearance rates and tissue distribution profiles than full length antibodies. Fc glycosylation is perceived to have a minimal effect on PK while that of terminal high mannose remains unclear. More investigation is warranted to determine if injection route and/or site impacts PK. Nonetheless, a better understanding of the effects of all these variations may allow for the better design of antibody therapeutics.
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Physicochemical properties including hydrated size, charge, hydrophobicity, electrophoretic mobility, isoelectric point, and glycosylation can potentially influence mAb PK.
“Physiochemical properties including hydrated size (Stokes radius), charge, hydrophobicity, electrophoretic mobility, isoelectric point (pI), and glycosylation can potentially influence mAb PK.38, 39”
From Tutorial on monoclonal antibody pharmacokinetics and its considerations in early development (2018) · cites this paper as [39]
Many factors, such as antibody properties (hydrophobicity, charge, glycosylation patterns), intersubject variability (disease status, body size, genetic polymorphisms, concomitant medication, comorbidities), and immune-mediated response generated by mAbs administration, can also impact mAb clearance.
“Many other factors, such as antibody properties (hydrophobicity, charge,38 glycosylation patterns39), intersubject variability (disease status, body size, genetic polymorphisms, concomitant medication, comorbidities, etc.40), and immune‐mediated response generated by mAbs administration can also impact mAb clearance.”
From Tutorial on monoclonal antibody pharmacokinetics and its considerations in early development (2018) · cites this paper as [39]
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References 40 · Cited by 119
Research works printed but not linked: 1
- Wang W, Wang EQ, Balthasar JP. Monoclonal antibody phar- macokinetics and pharmacodynamics. Clin Pharmacol Ther. 2008;84(5):548-58.
- Authors
- Bumbaca, D., Boswell, C. A., Fielder, P. J., & Khawli, L. A.
- Affiliations
- Genentech (US)
- Corresponding author
- Bumbaca, Daniela
- Venue
- The AAPS Journal
- Published
- 2012-05-18
- Volume
- 14
- Issue
- 3
- Pages
- 554-558
- ISSN
- 1550-7416 (ISSN-L)
- PMC
- PMC3385840
- OpenAlex
- W2094309883
- Cited by
- 119
- References
- 40
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 9 · 2023: 5 · 2022: 11 · 2021: 8 · 2020: 3 · 2019: 13 · 2018: 7 · 2017: 7 · 2016: 9 · 2015: 14 · 2014: 12 · 2013: 10 · 2012: 2
- FWCI
- 1.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- The AAPS Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
- Keywords
- monoclonal antibodies, pharmacokinetics, isoelectric point, antibody clearance, serum half-life, antibody fragments, Fc glycosylation, injection route, injection site, antibody design
- MeSH terms
- Antibodies, Glycosylation, Isoelectric Point
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