Teo Yi Ling

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obgtyl@nus.edu.sg


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    Pharmacokinetics of Prenylflavonoids following Oral Ingestion of Standardized Epimedium Extract in Humans
    (GEORG THIEME VERLAG KG, 2019-03-01) Teo, Yi Ling; Cheong, Wei Fun; Cazenave-Gassiot, Amaury; Ji, Shanshan; Logan, Susan; Lee, Zhi Xing Kelvin; Li, Jun; Seng, Kok Yong; Lee, Lawrence Soon-U; Yong, Eu Leong; Prof Eu Leong Yong; PHARMACOLOGY; MEDICINE; LIFE SCIENCES INSTITUTE; OBSTETRICS & GYNAECOLOGY
    Leaves of the Epimedium plant are traditionally consumed for bone health and other indications. The aim of this study was to establish the safety and pharmacokinetics of the metabolites of prenylflavonoids (icariin, icariside I, icariside II, icaritin, and desmethylicaritin) following single doses of a defined Epimedium prenylflavonoid extract in humans. A single oral dose of 370, 740, or 1110 mg of a standardized Epimedium prenylflavonoid extract was administered to 30 healthy male subjects in a randomized, placebo-controlled trial. Serum samples were collected over a 48-h period and analyzed by liquid chromatography-tandem mass spectrometry and non-compartmental pharmacokinetic modelling. Epimedium prenylflavonoid extracts were well tolerated and no adverse effects were observed. The principle metabolites detected in the serum were icariside II and desmethylicaritin. Icariside II had a T max of between 4.1-4.3 h, reaching a maximum AUC 0→∞ of 23.0 (17.5, 29.9) h×ng/mL (median [IQR: interquartile range]) with the highest dose of the Epimedium prenylflavonoid. On the other hand, desmethylicaritin had a delayed T max of 24.1-24.4 h and reached a maximum AUC 0→∞ of 126.1 (62.4, 202.9) h×ng/mL. The median maximum plasma concentration and AUC 0→∞ of desmethyliciaritin showed an increase with higher doses of the Epimedium prenylflavonoid (p < 0.05). Icariin, icariside I, and icaritin levels were below detection limits. Levels of Epimedium prenylflavonoid metabolites observed in this study were consistent with levels demonstrated to have anti-osteoporotic effects in cellular and animal studies. Coupled with the favorable safety profile of the extract observed, further studies are required to explore the utility of Epimedium prenylflavonoid extracts to prevent osteoporosis in postmenopausal women.