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Minipig as a potential translatable model for monoclonal antibody pharmacokinetics after intravenous and subcutaneous administration
Open accessAbstract
Subcutaneous (SC) delivery is a common route of administration for therapeutic monoclonal antibodies (mAbs) with pharmacokinetic (PK)/pharmacodynamic (PD) properties requiring long-term or frequent drug administration. An ideal in vivo preclinical model for predicting human PK following SC administration may be one in which the skin and overall physiological characteristics are similar to that of humans. In this study, the PK properties of a series of therapeutic mAbs following intravenous (IV) and SC administration in Göttingen minipigs were compared with data obtained previously from humans. The present studies demonstrated: (1) minipig is predictive of human linear clearance; (2) the SC bioavailabilities in minipigs are weakly correlated with those in human; (3) minipig mAb SC absorption rates are generally higher than those in human and (4) the SC bioavailability appears to correlate with systemic clearance in minipigs. Given the important role of the neonatal Fc-receptor (FcRn) in the PK of mAbs, the in vitro binding affinities of these IgGs against porcine, human and cynomolgus monkey FcRn were tested. The result showed comparable FcRn binding affinities across species. Further, mAbs with higher isoelectric point tended to have faster systemic clearance and lower SC bioavailability in both minipig and human. Taken together, these data lend increased support for the use of the minipig as an alternative predictive model for human IV and SC PK of mAbs.
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“Rodents and mini pig have also been explored to further understand the mechanism and variables in mAbs absorption.22”
From Tutorial on monoclonal antibody pharmacokinetics and its considerations in early development (2018) · cites this paper as [22]
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Metadata
- Authors
- Zheng, Y., Tesar, D. B., Benincosa, L., Birnböck, H., Boswell, C. A., Bumbaca, D., Cowan, K. J., Danilenko, D. M., Daugherty, A. L., Fielder, P. J., Grimm, H. P., Joshi, A., Justies, N., Kolaitis, G., Lewin-Koh, N., Li, J., McVay, S., O'Mahony, J., Otteneder, M., Pantze, M., Putnam, W. S., Qiu, Z. J., Ruppel, J., Singer, T., Stauch, O., Theil, F.-P., Visich, J., Yang, J., Ying, Y., Khawli, L. A., & Richter, W. F.
- Affiliations
- Genentech (US)
- F. Hoffmann-La Roche AG (CH)
- Corresponding author
- Khawli, Leslie A.
- Richter, Wolfgang F.
- ORCID
- Venue
- mAbs
- Publisher
- Informa UK Limited
- Published
- 2012-03
- Volume
- 4
- Issue
- 2
- Pages
- 243-255
- ISSN
- 1942-0862 (ISSN-L)
- 1942-0870
- PMC
- PMC3361660
- OpenAlex
- W1997578973
- Cited by
- 149
- References
- 60
- Citations by year
- 2026: 16 · 2025: 7 · 2024: 11 · 2023: 10 · 2022: 14 · 2021: 15 · 2020: 13 · 2019: 10 · 2018: 13 · 2017: 7 · 2016: 3 · 2015: 13 · 2014: 10 · 2013: 4 · 2012: 3
- FWCI
- 7.25
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- mAbs (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- F. Hoffmann-La Roche
- Genentech
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
- Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
- Keywords
- minipigs, monoclonal antibodies, pharmacokinetics, subcutaneous administration, intravenous administration, percutaneous absorption, systemic clearance, neonatal Fc receptor, isoelectric point, bioavailability, species comparison
- MeSH terms
- Animals, Antibodies, Monoclonal, Female, Humans, Injections, Subcutaneous, Male, Swine, Swine, Miniature, Models, Immunological, Administration, Intravenous
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