Use of Physiologically Based Pharmacokinetic Modeling to Predict Human Gut Microbial Conversion of Daidzein to S-Equol.

ABSTRACT: A physiologically based pharmacokinetic (PBPK) model was developed for daidzein and its metabolite S-equol. Anaerobic in vitro incubations of pooled fecal samples from S-equol producers and nonproducers allowed definition of the kinetic constants. PBPK model-based predictions for the maximum daidzein plasma concentration (C_max) were comparable to literature data. The predictions also revealed that the C_max of S-equol in producers was only up to 0.22% that of daidzein, indicating that despite its higher estrogenicity, S-equol is likely to contribute to the overall estrogenicity upon human daidzein exposure to a only limited extent. An interspecies comparison between humans and rats revealed that the catalytic efficiency for S-equol formation in rats was 210-fold higher than that of human S-equol producers. The described in vitro-in silico strategy provides a proof-of-principle on how to include microbial metabolism in humans in PBPK modeling as part of the development of new approach methodologies (NAMs).

SUBMITTER: Wang Q 

PROVIDER: S-EPMC8759082 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature