细胞色素P450变异对哌替啶的影响神经毒性代谢物normeperidine去。

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穆雷杰,美世SL,杰克逊KD

细胞色素P450变异对哌替啶的影响神经毒性代谢物normeperidine去。

2019 3月22:1-14 Xenobiotica。。doi: 10.1080 / 00498254.2019.1599465。

PubMed ID

30902024 (在PubMed

]

文摘

1。哌替啶去甲基化是一种阿片镇痛,经历形成了神经毒性代谢物normeperidine。先前的研究表明,哌替啶由细胞色素P450酶是催化去2 b6 (CYP2B6), CYP3A4和CYP2C19。2。本研究的目的是检查相对P450贡献哌替啶和评估CYP2C19多态性的影响去normeperidine一代。实验使用重组P450酶选择性化学抑制剂、酶动力学分析,和相关分析与个别CYP2C19-genotyped人类肝脏微粒体。3所示。哌替啶的催化效率(kcat /公里)去CYP2B6重组和CYP2C19之间的相似,但CYP3A4的明显降低。4所示。在人类肝微粒体,CYP2C19-genotyped normeperidine形成与CYP2C19显著相关活动(S-mephenytoin 4羟基化)。 5. CYP2C19 inhibitor (+)-N-3-benzylnirvanol and CYP3A inhibitor ketoconazole significantly reduced microsomal normeperidine generation by an individual donor with high CYP2C19 activity, whereas donors with lower CYP2C19 activity were sensitive to inhibition by ketoconazole but not benzylnirvanol. 6. These findings demonstrate that the relative CYP3A4, CYP2B6, and CYP2C19 involvement in meperidine N-demethylation depends on the enzyme activities in individual human liver microsomal samples. CYP2C19 is likely an important contributor to normeperidine generation in individuals with high CYP2C19 activity, but additional factors influence inter-individual metabolite accumulation.

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药物酶

药物	酶	类	生物	药理作用	行动
哌替啶	细胞色素P450 2 c19	蛋白质	人类	未知的	底物	细节