新陈代谢的一个新的局部麻醉,ropivacaine人类肝细胞色素P450。

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田中Furuichi Oda Y, K, K, Hiroi T, Imaoka年代,一个,藤森M, Funae Y

新陈代谢的一个新的局部麻醉,ropivacaine人类肝细胞色素P450。

麻醉学。1995年1月,82 (1):214 - 20。doi: 10.1097 / 00000542-199501000-00026。

PubMed ID

7832304 (在PubMed

]

文摘

背景:Ropivacaine是一个长时间的局部麻醉作用。虽然不如bupivacaine有毒,局部麻醉毒性可能当血浆浓度增加。因为ropivacaine amide-type局部麻醉,是由细胞色素P450 (P450)在肝脏代谢,消除和血浆浓度可以依赖P450的水平。这个调查的目的是为了阐明人类肝P450 ropivacaine的新陈代谢。方法:ropivacaine相比使用重组人类的新陈代谢和纯化鼠肝P450酶同功酶。一个使用抗体抑制研究老鼠使用肝微粒体P450执行从人类和老鼠发现了哪些P450参与ropivacaine新陈代谢。结果:Ropivacaine代谢2 ',6 ' -pipecoloxylidide (PPX), 3 ' -hydroxyropivacaine(3 ' -哦罗普)和4 ' -hydroxyropivacaine(4 ' -哦罗普)来自人类和大鼠的肝微粒体。PPX是人类和大鼠肝微粒体的主要代谢物。与鼠P450重组系统。PPX由CYP2C11和3 a2 4’-哦罗普CYP1A2和3 ' -哦罗普CYP1A2和2 d1。 Formation of PPX in rat hepatic microsomes was inhibited by anti CYP3A2, but not by CYP2C11 antibody, and formation of 3'-OH Rop was inhibited by CYP1A2 and 2D1 antibodies. Anti CYP3A2 and 1A2 antibodies inhibited the formation of PPX and 3'-OH Rop in human hepatic microsomes, respectively. Recombinant human P450s expressed in lymphoblast cells were used for further study. CYP3A4 and 1A2 formed the most PPX and 3'-OH Rop, respectively. Ropivacaine N-dealkylation and 3'-hydroxylation activities correlated well with the level of CYP3A4 and 1A2 in human hepatic microsomes, respectively. CONCLUSIONS: Ropivacaine was metabolized to PPX, 3'-OH Rop, and 4'-OH Rop by hepatic P450. PPX was a major metabolite in human hepatic microsomes. CYP3A4 was involved in producing PPX. CYP1A2 was involved in the formation of 3'-OH Rop in human hepatic microsomes.

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药物酶

药物	酶	类	生物	药理作用	行动
Ropivacaine	细胞色素P450 2 b6	蛋白质	人类	没有	底物	细节
Ropivacaine	细胞色素P450 3 a4	蛋白质	人类	未知的	底物	细节