Toward once-monthly insulin therapy via synergy in two pharmacokinetic protractors: Fc-conjugation and fatty acid acylation.
RSC Chem Biol
; 5(8): 763-775, 2024 Jul 31.
Article
em En
| MEDLINE
| ID: mdl-39092439
ABSTRACT
Pharmacokinetic properties and duration of therapeutic action of a pharmaceutical agent can be significantly extended through the combination of two distinct strategies aimed at increasing plasma half-life fatty acid acylation and Fc-conjugation. Using insulin as a case study, we demonstrate that a doubly protracted insulin analog produces a substantial prolongation of pharmacodynamic effect to lower blood glucose in STZ-treated mice when compared to the Fc-only counterparts. This enhancement is further corroborated by direct pharmacokinetic measurements in rat and dog models, demonstrating the potential for once-monthly insulin therapy. The results suggest that this approach might have broad application across a diverse spectrum of peptide- and protein-based therapeutics.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
RSC Chem Biol
Ano de publicação:
2024
Tipo de documento:
Article