Use of Physiologically Based Pharmacokinetic Modeling to Predict Human Gut Microbial Conversion of Daidzein to S-Equol
| Autor: | Ivonne M.C.M. Rietjens, Bert Spenkelink, Rungnapa Boonpawa, Qianrui Wang |
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| Rok vydání: | 2021 |
| Předmět: |
Physiologically based pharmacokinetic modelling
Metabolite S-equol Microbial metabolism Cmax Toxicology Article chemistry.chemical_compound Feces Human gut Pharmacokinetics Animals Humans Food science Toxicologie VLAG gut microbiota Chemistry Daidzein food and beverages General Chemistry Isoflavones Gastrointestinal Microbiome Rats Equol (S)-Equol daidzein General Agricultural and Biological Sciences physiologically based pharmacokinetic (PBPK) modeling |
| Zdroj: | Journal of Agricultural and Food Chemistry Journal of Agricultural and Food Chemistry, 70(1), 343-352 Journal of Agricultural and Food Chemistry 70 (2022) 1 |
| ISSN: | 1520-5118 0021-8561 |
| Popis: | 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 (Cmax) were comparable to literature data. The predictions also revealed that the Cmax 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). |
| Databáze: | OpenAIRE |
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