School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, China.
School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, China.
Chem Biol Interact. 2020 Aug 25;327:109146. doi: 10.1016/j.cbi.2020.109146. Epub 2020 Jun 17.
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.
吴茱萸（EF），是芸香科吴茱萸属植物石虎或疏毛吴茱萸的干燥近成熟果实，通常用于治疗头痛、腹痛、疝气和月经过多已有数千年的历史。据报道，它是一种通过代谢激活主要由 CYP3A 产生的轻度毒性草药，但几乎没有从药代动力学相互作用方面进行解释。本研究旨在探讨 CYP3A 诱导剂/抑制剂在 5 种生物碱（吴茱萸碱（EVOD）、吴茱萸卡品碱（RUTA）、1-甲基-2-十一烷基-4(1H)-喹啉酮（MUDQ）、1-甲基-2-壬基-4(1H)-喹啉酮（MNNQ）和吴茱萸卡品碱（EVOC））与 EF 肝毒性相关的药代动力学中的作用。结果表明，在 CYP3A 抑制剂存在的情况下，EF 中 5 种生物碱的代谢受到抑制，而在 CYP3A 诱导剂存在的情况下，EF 中 5 种生物碱的代谢得到促进。因此，当 EF 与 CYP3A 诱导剂联合使用时，需要注意剂量，因为药物代谢增强，可能导致毒性。
