赤道
大豆黄酮
基于生理学的药代动力学模型
代谢物
化学
异黄酮素
最大值
药代动力学
生物信息学
食品科学
染料木素
药理学
生物化学
生物
内分泌学
基因
作者
Qianrui Wang,Bert Spenkelink,Rungnapa Boonpawa,Ivonne M.C.M. Rietjens
标识
DOI:10.1021/acs.jafc.1c03950
摘要
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).
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