Induction of open-form bile canaliculus formation by hepatocytes for evaluation of biliary drug excretion.
Commun Biol
; 6(1): 866, 2023 08 22.
Article
em En
| MEDLINE
| ID: mdl-37608051
ABSTRACT
Biliary excretion is a major drug elimination pathway that affects their efficacy and safety. The currently available in vitro sandwich-cultured hepatocyte method is cumbersome because drugs accumulate in the closed bile canalicular lumen formed between hepatocytes and their amounts cannot be mealsured directly. This study proposes a hepatocyte culture model for the rapid evaluation of drug biliary excretion using permeation assays. When hepatocytes are cultured on a permeable support coated with the cell adhesion protein claudins, an open-form bile canalicular lumen is formed at the surface of the permeable support. Upon application to the basolateral (blood) side, drugs appear on the bile canalicular side. The biliary excretion clearance of several drugs, as estimated from the obtained permeabilities, correlates well with the reported in vivo biliary excretion clearance in humans. Thus, the established model is useful for applications in the efficient evaluation of biliary excretion during drug discovery and development.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Canalículos Biliares
/
Eliminação Hepatobiliar
Limite:
Humans
Idioma:
En
Revista:
Commun Biol
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Japão
País de publicação:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM