Biotransformation of Abiraterone Into Five Characteristic Metabolites by the Rat Gut Microbiota and Liver Microsomes

Adili Keranmu; Fei-Ya Yang; Wasilijiang Wahafu; Su-Jun Han; Guo-Sheng Yang; Nian-Zeng Xing

doi:10.3389/fonc.2022.890323

Biotransformation of Abiraterone Into Five Characteristic Metabolites by the Rat Gut Microbiota and Liver Microsomes

Front Oncol. 2022 Jul 22:12:890323. doi: 10.3389/fonc.2022.890323. eCollection 2022.

Authors

Adili Keranmu^{1

2}, Fei-Ya Yang¹, Wasilijiang Wahafu¹, Su-Jun Han¹, Guo-Sheng Yang², Nian-Zeng Xing^{1

3}

Affiliations

¹ 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.
² Department of Urology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
³ Department of Urology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, China.

Abstract

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 vitro. In this study, five metabolites (M1, M2, M3, M4 and M5) of Abiraterone were discovered using LC/MSⁿ-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.

Keywords: abiraterone; gut microbiota; liver microsome; metabolites; prostate cancer.