Quantitative pulmonary pharmacokinetics of tetrandrine for SARS-CoV-2 repurposing: a physiologically based pharmacokinetic modeling approach.

ABSTRACT: Tetrandrine (TET) has been traditionally used in China as a medication to treat silicosis and has recently demonstrated anti-SARS-CoV-2 potential in vitro. By recognizing the disparity between in vitro findings and in vivo performance, we aimed to estimate the free lung concentration of TET using a physiologically based pharmacokinetic (PBPK) model to link in vitro activity with in vivo efficacy. Comparative pharmacokinetic studies of TET were performed in rats and dogs to elucidate the pharmacokinetic mechanisms as well as discern interspecies variations. These insights facilitated the creation of an animal-specific PBPK model, which was subsequently translated to a human model following thorough validation. Following validation of the pharmacokinetic pr

SUBMITTER: Wang F 

PROVIDER: S-EPMC11427368 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature