Keranmu Adili, Yang Fei-Ya, Wahafu Wasilijiang, Han Su-Jun, Yang Guo-Sheng, Xing Nian-Zeng
State Key Laboratory of Molecular Oncology, Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Urology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Front Oncol. 2022 Jul 22;12:890323. doi: 10.3389/fonc.2022.890323. eCollection 2022.
It is well known that the role of gut microbiota in drug metabolism, especially in oral difficult absorbable drugs. Understanding the gut microbiota could enable us to understand drugs in new ways. The purpose of the study was to investigate explore the metabolites of the anti-prostate cancer drug Abiraterone by examining gut microbiota metabolism and hepatic metabolism . In this study, five metabolites (M1, M2, M3, M4 and M5) of Abiraterone were discovered using LC/MS-IT-TOF. Four isomeric metabolites M1-M4 were found in liver microsome. M5 was found in the intestinal contents of Sprague-Dawley rats with a molecular weight of 388.31. Among them, M4 was found to be Abiraterone N-Oxide by comparison with the standard sample. After further comparing the metabolic behavior of Abiraterone in rat gut microbiota and liver microsomes, we delineated the possible metabolic pathways of Abiraterone. In conclusion, Abiraterone is metabolized specifically in liver microsomes and gut microbiota. This study can provide a theoretical basis for elucidating the metabolic mechanism of Abiraterone and guide its rational application in clinic.
众所周知，肠道微生物群在药物代谢中发挥作用，尤其是在口服难吸收药物方面。了解肠道微生物群能够使我们以新的方式理解药物。本研究的目的是通过研究肠道微生物群代谢和肝脏代谢来探究抗前列腺癌药物阿比特龙的代谢产物。在本研究中，使用液相色谱/质谱-离子阱-飞行时间质谱仪发现了阿比特龙的五种代谢产物（M1、M2、M3、M4和M5）。在肝微粒体中发现了四种同分异构代谢产物M1-M4。在斯普拉格-道利大鼠的肠内容物中发现了分子量为388.31的M5。其中，通过与标准样品比较发现M4为阿比特龙N-氧化物。在进一步比较阿比特龙在大鼠肠道微生物群和肝微粒体中的代谢行为后，我们描绘了阿比特龙可能的代谢途径。总之，阿比特龙在肝微粒体和肠道微生物群中进行特异性代谢。本研究可为阐明阿比特龙的代谢机制提供理论依据，并指导其在临床中的合理应用。
