Factors contributing to the nonlinear pharmacokinetics of astegolimab: a close examination of potential causes.
Bioanalysis
; 15(21): 1305-1314, 2023 Nov.
Article
em En
| MEDLINE
| ID: mdl-37791725
ABSTRACT
Aim:
This paper describes a case study of an antibody therapeutic targeting a membrane-bound receptor, also present in systemic circulation, as a soluble receptor. During phase I studies of astegolimab, nonlinear pharmacokinetics (PKs) were observed. We investigated the potential contribution of antidrug antibodies, target-mediated drug disposition and assay format. Materials &methods:
A more target-tolerant assay was developed, and a subset of phase I samples were evaluated in both free and total PK assay formats. Results &conclusion:
Our results demonstrate that there were two main contributors to PK nonlinearity soluble target interference in the free PK assay, in addition to target-mediated drug disposition. Antidrug antibody status did not significantly impact PK.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Anticorpos Monoclonais Humanizados
/
Modelos Biológicos
Tipo de estudo:
Etiology_studies
Idioma:
En
Revista:
Bioanalysis
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos