Volume 45, Issue 3 pp. 149-158
ORIGINAL ARTICLE

Icaritin exhibits potential drug–drug interactions through the inhibition of human UDP-glucuronosyltransferase in vitro

Yi Rong

Yi Rong

Office of Pharmacotoxicology, Center for Drug Evaluation, NMPA, Beijing, China

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Nanxi Li

Nanxi Li

Beijing Institute of Radiation Medicine, Beijing, China

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Xuan Qiao

Xuan Qiao

Beijing Institute of Radiation Medicine, Beijing, China

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Lei Yang

Lei Yang

Beijing Institute of Radiation Medicine, Beijing, China

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Peng Han

Peng Han

Beijing Institute of Radiation Medicine, Beijing, China

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Zhiyun Meng

Zhiyun Meng

Beijing Institute of Radiation Medicine, Beijing, China

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Hui Gan

Hui Gan

Beijing Institute of Radiation Medicine, Beijing, China

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Zhuona Wu

Zhuona Wu

Beijing Institute of Radiation Medicine, Beijing, China

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Xiaoxia Zhu

Xiaoxia Zhu

Beijing Institute of Radiation Medicine, Beijing, China

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Yunbo Sun

Yunbo Sun

Beijing Institute of Radiation Medicine, Beijing, China

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Shuchen Liu

Shuchen Liu

Beijing Institute of Radiation Medicine, Beijing, China

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Guifang Dou

Guifang Dou

Beijing Institute of Radiation Medicine, Beijing, China

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Ruolan Gu

Corresponding Author

Ruolan Gu

Beijing Institute of Radiation Medicine, Beijing, China

Correspondence

Ruolan Gu, Beijing Institute of Radiation Medicine, Beijing 100850, China.

Email: [email protected]

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First published: 17 June 2024

Abstract

Icaritin is a prenylflavonoid derivative of the genus Epimedium (Berberidaceae) and has a variety of pharmacological actions. Icaritin is approved by the National Medical Products Administration as an anticancer drug that exhibits efficacy and safety advantages in patients with hepatocellular carcinoma cells. This study aimed to evaluate the inhibitory effects of icaritin on UDP-glucuronosyltransferase (UGT) isoforms. 4-Methylumbelliferone (4-MU) was employed as a probe drug for all the tested UGT isoforms using in vitro human liver microsomes (HLM). The inhibition potentials of UGT1A1 and 1A9 in HLM were further tested by employing 17β-estradiol (E2) and propofol (PRO) as probe substrates, respectively. The results showed that icaritin inhibits UGT1A1, 1A3, 1A4, 1A7, 1A8, 1A10, 2B7, and 2B15. Furthermore, icaritin exhibited a mixed inhibition of UGT1A1, 1A3, and 1A9, and the inhibition kinetic parameters (Ki) were calculated to be 3.538, 2.117, and 0.306 (μM), respectively. The inhibition of human liver microsomal UGT1A1 and 1A9 both followed mixed mechanism, with Ki values of 2.694 and 1.431 (μM). This study provides supporting information for understanding the drug–drug interaction (DDI) potential of the flavonoid icaritin and other UGT-metabolized drugs in clinical settings. In addition, the findings provide safety evidence for DDI when liver cancer patients receive a combination therapy including icaritin.

CONFLICT OF INTEREST STATEMENT

We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the manuscript entitled “Icaritin exhibits potential drug–drug interactions through the inhibition of human UDP-glucuronosyltransferase in vitro”.

DATA AVAILABILITY STATEMENT

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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