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Allometric scaling of therapeutic monoclonal antibodies in preclinical and clinical settings

Constant technological advancement enabled the production of therapeutic monoclonal antibodies (mAbs) and will continue to contribute to their rapid expansion. Compared to small-molecule drugs, mAbs have favorable characteristics, but also more complex pharmacokinetics (PK), e.g., target-mediated no...

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Autores principales: Germovsek, Eva, Cheng, Ming, Giragossian, Craig
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463036/
https://www.ncbi.nlm.nih.gov/pubmed/34530672
http://dx.doi.org/10.1080/19420862.2021.1964935
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author Germovsek, Eva
Cheng, Ming
Giragossian, Craig
author_facet Germovsek, Eva
Cheng, Ming
Giragossian, Craig
author_sort Germovsek, Eva
collection PubMed
description Constant technological advancement enabled the production of therapeutic monoclonal antibodies (mAbs) and will continue to contribute to their rapid expansion. Compared to small-molecule drugs, mAbs have favorable characteristics, but also more complex pharmacokinetics (PK), e.g., target-mediated nonlinear elimination and recycling by neonatal Fc-receptor. This review briefly discusses mAb biology, similarities and differences in PK processes across species and within human, and provides a detailed overview of allometric scaling approaches for translating mAb PK from preclinical species to human and extrapolating from adults to children. The approaches described here will remain vital in mAb drug development, although more data are needed, for example, from very young patients and mAbs with nonlinear PK, to allow for more confident conclusions and contribute to further growth of this field. Improving mAb PK predictions will facilitate better planning of (pediatric) clinical studies and enable progression toward the ultimate goal of expediting drug development.
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spelling pubmed-84630362021-09-25 Allometric scaling of therapeutic monoclonal antibodies in preclinical and clinical settings Germovsek, Eva Cheng, Ming Giragossian, Craig MAbs Review Constant technological advancement enabled the production of therapeutic monoclonal antibodies (mAbs) and will continue to contribute to their rapid expansion. Compared to small-molecule drugs, mAbs have favorable characteristics, but also more complex pharmacokinetics (PK), e.g., target-mediated nonlinear elimination and recycling by neonatal Fc-receptor. This review briefly discusses mAb biology, similarities and differences in PK processes across species and within human, and provides a detailed overview of allometric scaling approaches for translating mAb PK from preclinical species to human and extrapolating from adults to children. The approaches described here will remain vital in mAb drug development, although more data are needed, for example, from very young patients and mAbs with nonlinear PK, to allow for more confident conclusions and contribute to further growth of this field. Improving mAb PK predictions will facilitate better planning of (pediatric) clinical studies and enable progression toward the ultimate goal of expediting drug development. Taylor & Francis 2021-09-16 /pmc/articles/PMC8463036/ /pubmed/34530672 http://dx.doi.org/10.1080/19420862.2021.1964935 Text en © 2021 Taylor & Francis Group, LLC https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Germovsek, Eva
Cheng, Ming
Giragossian, Craig
Allometric scaling of therapeutic monoclonal antibodies in preclinical and clinical settings
title Allometric scaling of therapeutic monoclonal antibodies in preclinical and clinical settings
title_full Allometric scaling of therapeutic monoclonal antibodies in preclinical and clinical settings
title_fullStr Allometric scaling of therapeutic monoclonal antibodies in preclinical and clinical settings
title_full_unstemmed Allometric scaling of therapeutic monoclonal antibodies in preclinical and clinical settings
title_short Allometric scaling of therapeutic monoclonal antibodies in preclinical and clinical settings
title_sort allometric scaling of therapeutic monoclonal antibodies in preclinical and clinical settings
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463036/
https://www.ncbi.nlm.nih.gov/pubmed/34530672
http://dx.doi.org/10.1080/19420862.2021.1964935
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