Physiologically Based Pharmacokinetic (PBPK) Modeling for Predicting Brain Levels of Drug in Rat.

ABSTRACT: One of the main obstacles in neurological disease treatment is the presence of the blood-brain barrier. New predictive high-throughput screening tools are essential to avoid costly failures in the advanced phases of development and to contribute to the 3 Rs policy. The objective of this work was to jointly develop a new in vitro system coupled with a physiological-based pharmacokinetic (PBPK) model able to predict brain concentration levels of different drugs in rats. Data from in vitro tests with three different cells lines (MDCK, MDCK-MDR1 and hCMEC/D3) were used together with PK parameters and three scaling factors for adjusting the model predictions to the brain and plasma profiles of six model drugs. Later, preliminary quantitative structure-property relationships (QSPRs) were constru

SUBMITTER: Sanchez-Dengra B 

PROVIDER: S-EPMC8471455 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature