Chulabhorn International College of Medicine, Thammasat University, Pathum Thani 12120, Thailand.
Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University, Pathum Thani 12120, Thailand.
Drug Des Devel Ther. 2020 Apr 9;14:1401-1444. doi: 10.2147/DDDT.S221518. eCollection 2020.
Drug metabolism is one of the most important pharmacokinetic processes and plays an important role during the stage of drug development. The metabolite profile investigation is important as the metabolites generated could be beneficial for therapy or leading to serious toxicity. This systematic review aims to summarize the research articles relating to the metabolite profile investigation of conventional drugs and herb-derived compounds for cancer chemotherapy, to examine factors influencing metabolite profiling of these drugs/compounds, and to determine the relationship between therapeutic efficacy and toxicity of their metabolites. The literature search was performed through PubMed and ScienceDirect databases up to January 2019. Out of 830 published articles, 78 articles were included in the analysis based on pre-defined inclusion and exclusion criteria. Both phase I and II enzymes metabolize the anticancer agents/herb-derived compounds . The major phase I reactions include oxidation/hydroxylation and hydrolysis, while the major phase II reactions are glucuronidation, methylation, and sulfation. Four main factors were found to influence metabolite formation, including species, gender, and route and dose of drug administration. Some metabolites were identified as active or toxic metabolites. This information is critical for cancer chemotherapy and anticancer drug development.
药物代谢是最重要的药代动力学过程之一，在药物开发阶段发挥着重要作用。代谢物谱研究很重要，因为生成的代谢物可能对治疗有益或导致严重的毒性。本系统综述旨在总结与癌症化疗用常规药物和草药化合物的代谢物谱研究相关的研究文章，考察影响这些药物/化合物代谢物谱分析的因素，并确定其代谢物治疗效果与毒性之间的关系。文献检索通过 PubMed 和 ScienceDirect 数据库进行，截至 2019 年 1 月。在 830 篇已发表的文章中，根据预先确定的纳入和排除标准，有 78 篇文章被纳入分析。I 期和 II 期酶均代谢抗癌药物/草药化合物。主要的 I 期反应包括氧化/羟化和水解，而主要的 II 期反应是葡萄糖醛酸化、甲基化和硫酸化。发现有四个主要因素影响代谢物的形成，包括物种、性别以及药物给药途径和剂量。一些代谢物被鉴定为活性或毒性代谢物。这些信息对于癌症化疗和抗癌药物开发至关重要。
