Cited by 149Monoclonal and Polyclonal Antibodies ResearchBiosimilars and Bioanalytical MethodsAnimal testing and alternatives

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Minipig as a potential translatable model for monoclonal antibody pharmacokinetics after intravenous and subcutaneous administration

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Zheng, Yanan, Tesar, Devin B., Benincosa, Lisa, Birnböck, Herbert, Boswell, C. Andrew, Bumbaca, Daniela, Cowan, Kyra J, Danilenko, Dimitry M., Daugherty, Ann L., Fielder, Paul J., Grimm, Hans Peter, Joshi, Amita, Justies, Nicole, Kolaitis, Gerry, Lewin-Koh, Nicholas, Li, Jing, McVay, Sami, O'Mahony, Jennifer, Otteneder, Michael, Pantze, Michael, Putnam, Wendy S., Qiu, Zhihua J., Ruppel, Jane, Singer, Thomas, Stauch, Oliver, Theil, Frank-Peter, Visich, Jennifer, Yang, Jihong, Ying, Yong, Khawli, Leslie A., Richter, Wolfgang F.·2012·mAbs

DOI 10.4161/mabs.4.2.19387PMC PMC3361660

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Abstract

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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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: Zheng, Yanan
Tesar, Devin B.
Boswell, C. Andrew
Cowan, Kyra J
Danilenko, Dimitry M.
Grimm, Hans Peter
Joshi, Amita
Justies, Nicole
Li, Jing
Otteneder, Michael
Putnam, Wendy S.
Qiu, Zhihua J.
Ruppel, Jane
Theil, Frank-Peter
Yang, Jihong
Ying, Yong
Khawli, Leslie A.
Richter, Wolfgang F.
Venue: mAbs
Publisher: Informa UK Limited
Published: 2012-03
Volume: 4
Issue: 2
Pages: 243-255
ISSN: 1942-0862 (ISSN-L)
1942-0870
DOI: 10.4161/mabs.4.2.19387
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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Minipig as a potential translatable model for monoclonal antibody pharmacokinetics after intravenous and subcutaneous administration

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