Application of a new MDCKII-MDR1 cell model to measure the extent of drug distribution in vitro at equilibrium for prediction of in vivo unbound brain-to-plasma drug distribution.

ABSTRACT:

Intro

Reliable estimates of drug uptake from blood to brain parenchyma are crucial in CNS drug discovery and development. While in vivo K_p,uu,brain estimates are the gold standard for investigating brain drug disposition, animal usage is a limitation to high throughput application. This study investigates an in vitro model using P-gp expressing MDCKII-MDR1 cells for predicting in vivo brain drug penetration.

Methods

In vitro equilibrium distribution studies were conducted in apical and basolateral solutions with high protein content to estimate K_p,brain and K_p,uu,brain values. The correlation between in vitro and in vivo K_p,brain values for a set of compounds was examined.

Results

We observed a good correlation between in vi

SUBMITTER: Langthaler K 

PROVIDER: S-EPMC10809502 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature