Allometric scaling of therapeutic monoclonal antibodies in preclinical and clinical settings.
MAbs
; 13(1): 1964935, 2021.
Article
em En
| MEDLINE
| ID: mdl-34530672
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Antineoplásicos Imunológicos
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Anticorpos Monoclonais
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Child
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Humans
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Newborn
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article