Comparable Intestinal and Hepatic First-Pass Effect of YL-IPA08 on the Bioavailability and Effective Brain Exposure, a Rapid Anti-PTSD and Anti-Depression Compound.

ABSTRACT: YL-IPA08, exerting rapid antidepressant-like and anxiolytic-like effects on behaviors by translocator protein (TSPO) mediation, is a novel compound that has been discovered and developed at our institute. Fit-for-purpose pharmacokinetic properties is urgently needed to be discovered as early as possible for a new compound. YL-IPA08 exhibited low bioavailability (∼6%) during the preliminary pharmacokinetics study in rats after oral administration. Our aim was to determine how metabolic disposition by microsomal P450 enzymes in liver and intestine limited YL-IPA08's bioavailability and further affected brain penetration to the target. Studies of in vitro metabolic stability and permeability combined with in vivo oral bioavailability, panel CYP inhibitor co-administration via di

SUBMITTER: Gao Y 

PROVIDER: S-EPMC7732531 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature