期刊
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
卷 12, 期 10, 页码 1264-1280出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/187152012803833107
关键词
Genistein; Flavonoids; Isoflavone; Bioavailability; Pharmacokinetics; ADME; Metabolism; Transporter; BCRP
资金
- National Institute of Health [GM070737]
Genistein, one of the most active natural flavonoids, exerts various biological effects including chemoprevention, antioxidation, antiproliferation and anticancer. More than 30 clinical trials of genistein with various disease indications have been conducted to evaluate its clinical efficacy. Based on many animals and human pharmacokinetic studies, it is well known that the most challenge issue for developing genistein as a chemoprevention agent is the low oral bioavailability, which may be the major reason relating to its ambiguous therapeutic effects and large interindividual variations in clinical trials. In order to better correlate pharmacokinetic to pharmacodynamics results in animals and clinical studies, an in-depth understanding of pharmacokinetic behavior of genistein and its ADME properties are needed. Numerous in vitro/in vivo ADME studies had been conducted to reveal the main factors contributing to the low oral bioavailability of genistein. Therefore, this review focuses on summarizing the most recent progress on mechanistic studies of genistein ADME and provides a systemic view of these processes to explain genistein pharmacokinetic behaviors in vivo. The better understanding of genistein ADME property may lead to development of proper strategy to improve genistein oral bioavailability via mechanism-based approaches.
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