Use of Physiologically Based Pharmacokinetic Modeling to Predict Human Gut Microbial Conversion of Daidzein to S-Equol
Qianrui Wang, Bert Spenkelink, Rungnapa Boonpawa, Ivonne M.C.M. Rietjens
Abstract
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).
Topics & Concepts
EquolDaidzeinPhysiologically based pharmacokinetic modellingMetaboliteChemistryIsoflavonesCmaxIn silicoPharmacokineticsFood scienceGenisteinBiochemistryPharmacologyBiologyEndocrinologyGenePhytoestrogen effects and researchTea Polyphenols and EffectsFood Quality and Safety Studies