Abstract Context: Cepharanthine (CEP) extracted from the roots of Stephania cepharantha Hayata (Menispermaceae), has a range of therapeutic potential in clinical conditions. Whether it affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. Materials and methods: The effects of CEP (100 μM) on eight human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8) were investigated in vitro using human liver microsomes (HLMs) with specific probe actions and probe substrates. In addition, the enzyme kinetic parameters were calculated. Results: The results showed that the activity of CYP3A4, CYP2E1 and CYP2C9 was inhibited by CEP, with IC50 values of 16.29, 25.62 and 24.57 μM, respectively, but other CYP isoforms were not affected. Enzyme kinetic studies showed that CEP was not only a non-competitive inhibitor of CYP3A4 but also a competitive inhibitor of CYP2E1 and CYP2C9, with Ki values of 8.12, 11.78 and 13.06 μM, respectively. Additionally, CEP is a time-dependent inhibitor for CYP3A4 with KI/Kinact value of 10.84/0.058 min/μM. Discussion and conclusions: The in vitro studies of CEP with CYP isoforms indicate that CEP has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP3A4, CYP2E1 and CYP2C9. Further clinical studies are needed to evaluate the significance of this interaction.

中文翻译：

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头孢氨苄对人肝细胞色素P450酶的体外抑制作用

摘要背景：从 Stephania cepharantha Hayata (Menispermaceae) 的根中提取的 Cepharanthine (CEP) 在临床条件下具有一系列治疗潜力。它是否影响人肝细胞色素 P450 (CYP) 酶的活性尚不清楚。材料和方法：使用具有特异性的人肝微粒体 (HLM) 在体外研究 CEP (100 μM) 对八种人肝脏 CYP 同工型（即 1A2、3A4、2A6、2E1、2D6、2C9、2C19 和 2C8）的影响探针动作和探针基板。此外，还计算了酶动力学参数。结果：结果显示CYP3A4、CYP2E1和CYP2C9的活性被CEP抑制，IC50值分别为16.29、25.62和24.57 μM，但其他​​CYP亚型不受影响。酶动力学研究表明，CEP 不仅是 CYP3A4 的非竞争性抑制剂，也是 CYP2E1 和 CYP2C9 的竞争性抑制剂，Ki 值分别为 8.12、11.78 和 13.06 μM。此外，CEP 是 CYP3A4 的时间依赖性抑制剂，KI/Kinact 值为 10.84/0.058 min/μM。讨论和结论：CEP 与 CYP 同种型的体外研究表明，CEP 有可能与其他经 CYP3A4、CYP2E1 和 CYP2C9 代谢的共同给药药物引起药代动力学药物相互作用。需要进一步的临床研究来评估这种相互作用的重要性。讨论和结论：CEP 与 CYP 同种型的体外研究表明，CEP 有可能与其他经 CYP3A4、CYP2E1 和 CYP2C9 代谢的共同给药药物引起药代动力学药物相互作用。需要进一步的临床研究来评估这种相互作用的重要性。讨论和结论：CEP 与 CYP 同种型的体外研究表明，CEP 有可能与其他经 CYP3A4、CYP2E1 和 CYP2C9 代谢的共同给药药物引起药代动力学药物相互作用。需要进一步的临床研究来评估这种相互作用的重要性。