Icaritin exhibits potential drug–drug interactions through the inhibition of human UDP-glucuronosyltransferase in vitro
Yi Rong
Office of Pharmacotoxicology, Center for Drug Evaluation, NMPA, Beijing, China
Search for more papers by this authorNanxi Li
Beijing Institute of Radiation Medicine, Beijing, China
Search for more papers by this authorXuan Qiao
Beijing Institute of Radiation Medicine, Beijing, China
Search for more papers by this authorLei Yang
Beijing Institute of Radiation Medicine, Beijing, China
Search for more papers by this authorPeng Han
Beijing Institute of Radiation Medicine, Beijing, China
Search for more papers by this authorZhiyun Meng
Beijing Institute of Radiation Medicine, Beijing, China
Search for more papers by this authorHui Gan
Beijing Institute of Radiation Medicine, Beijing, China
Search for more papers by this authorZhuona Wu
Beijing Institute of Radiation Medicine, Beijing, China
Search for more papers by this authorXiaoxia Zhu
Beijing Institute of Radiation Medicine, Beijing, China
Search for more papers by this authorYunbo Sun
Beijing Institute of Radiation Medicine, Beijing, China
Search for more papers by this authorShuchen Liu
Beijing Institute of Radiation Medicine, Beijing, China
Search for more papers by this authorGuifang Dou
Beijing Institute of Radiation Medicine, Beijing, China
Search for more papers by this authorCorresponding Author
Ruolan Gu
Beijing Institute of Radiation Medicine, Beijing, China
Correspondence
Ruolan Gu, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Email: [email protected]
Search for more papers by this authorYi Rong
Office of Pharmacotoxicology, Center for Drug Evaluation, NMPA, Beijing, China
Search for more papers by this authorNanxi Li
Beijing Institute of Radiation Medicine, Beijing, China
Search for more papers by this authorXuan Qiao
Beijing Institute of Radiation Medicine, Beijing, China
Search for more papers by this authorLei Yang
Beijing Institute of Radiation Medicine, Beijing, China
Search for more papers by this authorPeng Han
Beijing Institute of Radiation Medicine, Beijing, China
Search for more papers by this authorZhiyun Meng
Beijing Institute of Radiation Medicine, Beijing, China
Search for more papers by this authorHui Gan
Beijing Institute of Radiation Medicine, Beijing, China
Search for more papers by this authorZhuona Wu
Beijing Institute of Radiation Medicine, Beijing, China
Search for more papers by this authorXiaoxia Zhu
Beijing Institute of Radiation Medicine, Beijing, China
Search for more papers by this authorYunbo Sun
Beijing Institute of Radiation Medicine, Beijing, China
Search for more papers by this authorShuchen Liu
Beijing Institute of Radiation Medicine, Beijing, China
Search for more papers by this authorGuifang Dou
Beijing Institute of Radiation Medicine, Beijing, China
Search for more papers by this authorCorresponding Author
Ruolan Gu
Beijing Institute of Radiation Medicine, Beijing, China
Correspondence
Ruolan Gu, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Email: [email protected]
Search for more papers by this authorAbstract
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”.
Open Research
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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