Effect of CYP3A inducer/inhibitor on pharmacokinetics of five alkaloids in Evodiae Fructus
Effect of CYP3A inducer/inhibitor on pharmacokinetics of five alkaloids in Evodiae Fructus
复制标题
CYP3A诱导剂/抑制剂对吴茱萸5种生物碱药动学的影响
DOI：
10.1016/j.cbi.2020.109146
复制
发表时间：
2020
影响因子：
5.1
通讯作者：
Liu Xiaoqiu
中科院分区：
文献类型：
--
作者：
Zhang Wei;Guo Jingyan;Wang Dongmei;Ren Shumeng;Hua Huiming;Morikawa Toshio;Pan Yingni;Liu Xiaoqiu
吴茱萸（EvocalumFructus，EF）为芸香科植物Tetradium ruticarpum（A. Juss.）T.G.哈特利，通常用于治疗头痛，腹痛，疝气和月经过多数千年。据报道，它是一种轻度毒性的草药，主要通过CYP 3A代谢活化，但几乎没有从药代动力学相互作用中解释。本研究旨在探讨CYP 3A诱导剂/抑制剂在与EF肝毒性相关的5种生物碱（吴茱萸碱（EVOD）、吴茱萸次碱（RUTA）、1-甲基-2-十一烷基-4（1H）-喹诺酮（MUDQ）、1-甲基-2-壬基-4（1H）-喹诺酮（MNNQ）和吴茱萸次碱（EVOC））在Sprague道利（SD）大鼠体内药代动力学中的作用。结果表明，CYP 3A抑制剂抑制了EF中5种生物碱的代谢，而CYP 3A诱导剂促进了EF中5种生物碱的代谢。因此，当EF与CYP 3A诱导剂联合使用时，需要注意剂量，因为药物代谢会增强，这可能导致毒性。
Evodiae Fructus (EF), the dried nearly mature scented fruit of Tetradium ruticarpum (A.Juss.) T.G.Hartley, was typically used to treat headache, abdominal pain, hernias, and menorrhagia for thousands of years. It had been reported to be a mild toxic herb through metabolic activation mainly by CYP3A but was barely explained from pharmacokinetic interaction. The aim of the study was to investigate the role of CYP3A inducer/inhibitor in pharmacokinetics of five alkaloids (evodiamine (EVOD), rutaecarpine (RUTA), 1-methyl-2-undecyl-4(1H)-quinolone (MUDQ), 1-methyl-2-nonyl-4(1H)-quinolone (MNNQ) and evocarpine (EVOC)) associated with hepatotoxicity of EF in Sprague Dawley (SD) rats. The results demonstrated that the metabolism of the five alkaloids of.EF were inhibited in presence of CYP3A inhibitor whereas the metabolism of the five alkaloids of EF were promoted in presence of CYP3A inducer. Therefore, the dose is required attention when EF is taken in conjunction with CYP3A inducer as there is an enhancement in drug metabolism, which might lead to toxicity.