Induction of open-form bile canaliculus formation by hepatocytes for evaluation of biliary drug excretion.

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 p

SUBMITTER: Arakawa H 

PROVIDER: S-EPMC10444810 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature