Department of Pharmacology, Hebei Medical University, Key Laboratory of Pharmacology and Toxicology for New Drug, Hebei Province, 361 East Zhongshan Road, Shijiazhuang 050017, China; School of Pharmacy, Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang 050017, China.
School of Pharmacy, Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang 050017, China.
Environ Toxicol Pharmacol. 2014 Nov;38(3):901-12. doi: 10.1016/j.etap.2014.08.019. Epub 2014 Sep 30.
This study aimed to identify the specific cytochrome P450 (CYP450) enzymes involved in the metabolism of dipfluzine hydrochloride using the combination of a chemical inhibition study, a correlation analysis and a panel of recombinant rat CYP450 enzymes. The incubation of Dip with rat liver microsomes yielded four metabolites, which were identified by liquid chromatography-coupled tandem mass spectrometry (LC/MS/MS). The results from the assays involving eight selective inhibitors indicated that CYP3A and CYP2A1 contributed most to the metabolism of Dip, followed by CYP2C11, CYP2E1 and CYP1A2; however, CYP2B1, CYP2C6 and CYP2D1 did not contribute to the formation of the metabolites. The results of the correlation analysis and the assays involving the recombinant CYP450 enzymes further confirmed the above results and concluded that CYP3A2 contributed more than CYP3A1. The results will be valuable in understanding drug-drug interactions when Dip is coadministered with other drugs.
本研究旨在通过化学抑制研究、相关分析和一组重组大鼠 CYP450 酶，确定盐酸二氟嗪代谢中涉及的特定细胞色素 P450（CYP450）酶。将 Dip 与大鼠肝微粒体孵育生成了四种代谢物，通过液相色谱-串联质谱法（LC/MS/MS）进行了鉴定。涉及 8 种选择性抑制剂的测定结果表明，CYP3A 和 CYP2A1 对 Dip 的代谢贡献最大，其次是 CYP2C11、CYP2E1 和 CYP1A2；然而，CYP2B1、CYP2C6 和 CYP2D1 并未参与代谢物的生成。相关分析和涉及重组 CYP450 酶的测定结果进一步证实了上述结果，并得出 CYP3A2 的贡献大于 CYP3A1 的结论。这些结果对于理解 Dip 与其他药物同时使用时的药物相互作用将具有重要价值。
