Department of Neonatology, Yidu Central Hospital of Weifang , Weifang , Shandong , China.
Department of Pediatric Medicine, Yidu Central Hospital of Weifang , Weifang , Shandong , China.
Pharm Biol. 2019 Dec;57(1):571-576. doi: 10.1080/13880209.2019.1656257.
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. This study investigates the effects of KF on eight major CYP isoforms in human liver microsomes (HLMs). , HLMs were used to investigate the inhibitory effects of KF (100 μM) 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 (0-50 μM of KF) were conducted to determine the inhibition mode of KF on CYP enzymes. The results showed that KF inhibited the activity of CYP1A2, 3A4, and 2C9, with IC values of 20.56, 13.87, and 14.62 μM, 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 values of 7.11, 10.24, and 7.58 μM, respectively. In addition, KF is a time-dependent inhibitor for CYP3A4 with / value of 10.85/0.036 min/μM. The 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. 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.
山奈酚-3-O-芸香糖苷（KF）是一种具有生物活性的类黄酮，具有多种药理活性。然而，KF 是否影响人肝细胞色素 P450（CYP）酶的活性尚不清楚。本研究探讨了 KF 对人肝微粒体（HLMs）中 8 种主要 CYP 同工酶的影响。使用 HLMs 研究 KF（100μM）对 8 种人肝 CYP 同工酶（即 1A2、3A4、2A6、2E1、2D6、2C9、2C19 和 2C8）的抑制作用，并使用相应的探针底物。进行酶动力学研究（0-50μM 的 KF）以确定 KF 对 CYP 酶的抑制模式。结果表明，KF 抑制 CYP1A2、3A4 和 2C9 的活性，IC 值分别为 20.56、13.87 和 14.62μM，而其他 CYP 同工酶不受影响。酶动力学研究表明，KF 不仅是 CYP3A4 的非竞争性抑制剂，还是 CYP1A2 和 2C9 的竞争性抑制剂， 值分别为 7.11、10.24 和 7.58μM。此外，KF 是 CYP3A4 的时间依赖性抑制剂， 值为 10.85/0.036min/μM。KF 与 CYP 同工酶的研究表明，KF 有可能与其他同时服用的由 CYP1A2、3A4 和 2C9 代谢的药物发生药代动力学药物相互作用。建议不要将 KF 与由 CYP1A2、3A4 和 2C9 代谢的其他药物一起使用。需要进一步的临床研究来评估这种相互作用的意义。
