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Cross-species/cross-modality physiologically based pharmacokinetics for biologics: 89Zr-labelled albumin-binding domain antibody GSK3128349 in humans.
Sepp, Armin; Bergström, Mats; Davies, Marie.
Afiliação
  • Sepp A; IVIVT Modeling and Simulation, GlaxoSmithKline Plc , Stevenage, UK.
  • Bergström M; Cell Therapy RU, GlaxoSmithKline Plc , Stevenage, UK.
  • Davies M; Research CPEM, GlaxoSmithKline Plc , Stevenage, UK.
MAbs ; 12(1): 1832861, 2020.
Article em En | MEDLINE | ID: mdl-33073698
ABSTRACT
Two-pore physiologically-based pharmacokinetics (PBPK) for biologics describes the tissue distribution and elimination kinetics of soluble proteins as a function of their hydrodynamic radius and the physiological properties of the organs. Whilst many studies have been performed in rodents to parameterize the PBPK framework in terms of organ-specific lymph flow rates, similar validation in humans has been limited. This is mainly due to the paucity of the tissue distribution time course data for biologics that is not distorted by target-related binding. Here, we demonstrate that a PBPK model based on rodent data provided good to satisfactory extrapolation to the tissue distribution time course of 89Zr-labeled albumin-binding domain antibody (AlbudAb™) GSK3128349 in healthy human volunteers, including correct prediction of albumin-like plasma half-life, volume of distribution, and extravasation half-life. The AlbudAb™ used only binds albumin, and hence it also provides information about the tissue distribution kinetics and turnover of that ubiquitous and multifunctional plasma protein.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Radioisótopos / Zircônio / Albumina Sérica Humana / Modelos Biológicos / Anticorpos Monoclonais Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: MAbs Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Radioisótopos / Zircônio / Albumina Sérica Humana / Modelos Biológicos / Anticorpos Monoclonais Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: MAbs Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Reino Unido