%0 Journal Article
%T In vitro inhibitory effects of kaempferitrin on human liver cytochrome P450 enzymes
%A Jing Liu
%A Ning Zhang
%A Wenwen Dou
%A Zhixia Chen
%J Pharmaceutical Biology
%D 2019
%R https://doi.org/10.1080/13880209.2019.1656257
%X Abstract Context: Kaempferitrinis (KF) is a bioactive flavonoid and possesses numerous pharmacological activities. However, whether KF affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. Objective: This study investigates the effects of KF on eight major CYP isoforms in human liver microsomes (HLMs). Materials and methods: In vitro, HLMs were used to investigate the inhibitory effects of KF (100£¿¦ÌM) on the eight human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19, and 2C8), and corresponding probe substrates were used. Enzyme kinetic studies (0¨C50£¿¦ÌM of KF) were conducted to determine the inhibition mode of KF on CYP enzymes. Results: The results showed that KF inhibited the activity of CYP1A2, 3A4, and 2C9, with IC50 values of 20.56, 13.87, and 14.62£¿¦ÌM, respectively, but that other CYP isoforms were not affected. Enzyme kinetic studies showed that KF was not only a noncompetitive inhibitor of CYP3A4, but also a competitive inhibitor of CYP1A2 and 2C9, with Ki values of 7.11, 10.24, and 7.58£¿¦ÌM, respectively. In addition, KF is a time-dependent inhibitor for CYP3A4 with KI/Kinact value of 10.85/0.036£¿min/¦ÌM. Discussion: The in vitro studies of KF with CYP isoforms indicate that KF has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP1A2, 3A4, and 2C9. Conclusion: It is recommended that KF should not be used with other drugs metabolized by CYP1A2, 3A4, and 2C9. Further clinical studies are needed to evaluate the significance of this interaction
%U https://www.tandfonline.com/doi/full/10.1080/13880209.2019.1656257