Department of Pharmacy, Xijing Hospital of the Fourth Military Medical University, 17 Changlexi Street, Xi'an 710032, Shaanxi, China.
Biomed Pharmacother. 2012 Jun;66(4):318-21. doi: 10.1016/j.biopha.2012.01.001. Epub 2012 Feb 17.
The purpose of this study was to assess the potential inhibitory and inductive effects of felotaxel on cytochrome P450 isozymes in vitro. The inhibitory effects of felotaxel on various CYP isozymes were determined in human liver microsomes. In addition, the ability of felotaxel to induce CYP enzymes in cultured human hepatocytes was evaluated. Results showed that felotaxel did not inhibit CYP1A2-, CYP2C9-, CYP2C19-, CYP2E1-, CYP2D6-, CYP2B6-, CYP2C8-, and mediated activities in human liver microsomes up to a concentration of 100 μM, while the inhibition (<30% inhibition) of CYP3A4 activities was observed at 100 μM felotaxel. In vitro felotaxel did not induce CYP1A2, CYP2C19, or CYP3A4/5 activities in cultured human hepatocytes. In present study, felotaxel has been identified as a potent inhibitor of metabolic activity of CYP3A4. Therefore, clinically relevant pharmacokinetic drug-drug interactions are likely to occur between felotaxel and co-administered substrates of these CYP3A4 isozymes. These findings provided some useful information for safe and effective use of felotaxel in clinical practice.
本研究旨在评估氟他胺在体外对细胞色素 P450 同工酶的潜在抑制和诱导作用。在人肝微粒体中测定了氟他胺对各种 CYP 同工酶的抑制作用。此外，还评估了氟他胺在培养的人肝细胞中诱导 CYP 酶的能力。结果表明，氟他胺在 100μM 浓度下不抑制 CYP1A2、CYP2C9、CYP2C19、CYP2E1、CYP2D6、CYP2B6、CYP2C8 和介导的人肝微粒体活性，而 CYP3A4 活性的抑制（<30%抑制）在 100μM 氟他胺时观察到。在体外，氟他胺在培养的人肝细胞中不诱导 CYP1A2、CYP2C19 或 CYP3A4/5 活性。在本研究中，氟他胺已被鉴定为 CYP3A4 代谢活性的强抑制剂。因此，氟他胺与这些 CYP3A4 同工酶的同时给予的底物之间可能发生临床相关的药代动力学药物相互作用。这些发现为氟他胺在临床实践中的安全有效使用提供了一些有用的信息。
