The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
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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Cites
Physiological Parameters in Laboratory Animals and Humans
Davies, B., & Morris, T. (1993) · Pharmaceutical Research · doi:10.1023/a:1018943613122 · Cited by 2,930
FcRn: the neonatal Fc receptor comes of age
Roopenian, D. C., & Akilesh, S. (2007) · Nature Reviews Immunology · doi:10.1038/nri2155 · Cited by 2,346
Elimination mechanisms of therapeutic monoclonal antibodies
Tabrizi, M. A., Tseng, C.-M. L., & Roskos, L. K. (2006) · Drug Discovery Today · doi:10.1016/s1359-6446(05)03638-x · Cited by 479
Methods for in vitro percutaneous absorption studies II. Animal models for human skin
Bronaugh, R. L., Stewart, R. F., & Congdon, E. R. (1982) · Toxicology and Applied Pharmacology · doi:10.1016/0041-008x(82)90149-1 · Cited by 462
Effects of Charge on Antibody Tissue Distribution and Pharmacokinetics
Boswell, C. A., Tesar, D. B., Mukhyala, K., Theil, F.-P., Fielder, P. J., & Khawli, L. A. (2010) · Bioconjugate Chemistry · doi:10.1021/bc100261d · Cited by 398
Self-citationSuzuki, T., Ishii‐Watabe, A., Tada, M., Kobayashi, T., Kanayasu‐Toyoda, T., Kawanishi, T., & Yamaguchi, T. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903296 · Cited by 375
Frost, G. I. (2007) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.4.4.427 · Cited by 323
Petkova, S. B., Akilesh, S., Sproule, T. J., Christianson, G. J., Khabbaz, H. J. A., Brown, A. C., Presta, L. G., Meng, Y. G., & Roopenian, D. C. (2006) · International Immunology · doi:10.1093/intimm/dxl110 · Cited by 319
Deng, R., Iyer, S., Theil, F.-P., Mortensen, D. L., Fielder, P. J., & Prabhu, S. (2011) · mAbs · doi:10.4161/mabs.3.1.13799 · Cited by 285
Self-citationNeonatal FcR Expression in Bone Marrow-Derived Cells Functions to Protect Serum IgG from Catabolism
Akilesh, S., Christianson, G. J., Roopenian, D. C., & Shaw, A. S. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.7.4580 · Cited by 269
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Research works printed but not linked: 6
- McDonald TA, 2010, Curr Opin Mol Ther, 12, 461
- Washer G, 2008, Minipigs as an alternative non-rodent species in toxicology and safety studies
- Penninks A, 2011, Society of Toxicology
- Berk DA, 1996, Am J Physiol, 270, 330
- Fischer M, 1996, Am J Physiol, 270, 358
- den Broeder A, 2002, J Rheumatol, 29, 2288
Cited by
Sorted by citations
Pharmacokinetics of Monoclonal Antibodies
Ryman, J. T., & Meibohm, B. (2017) · CPT Pharmacometrics & Systems Pharmacology · doi:10.1002/psp4.12224 · Cited by 847
Physicochemical Stability of Monoclonal Antibodies: A Review
Basle, Y. L., Chennell, P., Tokhadzé, N., Astier, A., & Sautou, V. (2019) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2019.08.009 · Cited by 460
Pharmacokinetics of monoclonal antibodies and Fc-fusion proteins
Liming, L. (2017) · Protein & Cell · doi:10.1007/s13238-017-0408-4 · Cited by 407
Mechanistic Determinants of Biotherapeutics Absorption Following SC Administration
Richter, W. F., Bhansali, S. G., & Morris, M. E. (2012) · The AAPS Journal · doi:10.1208/s12248-012-9367-0 · Cited by 377
Self-citationTutorial on monoclonal antibody pharmacokinetics and its considerations in early development
Ovacik, M., & Lin, K. (2018) · Clinical and Translational Science · doi:10.1111/cts.12567 · Cited by 299
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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