Highly selective N-glucuronidation of four piperazine-containing drugs by UDP-glucuronosyltransferase 2B10
文献类型：期刊论文
| 作者 | Danyi Lu; Dong Dong; Baojian Wu |
| 刊名 | Expert Opinion on Drug Metabolism & Toxicology
 |
| 出版日期 | 2018 |
| 文献子类 | 期刊论文 |
| 英文摘要 | BACKGROUND: N-glucuronidation is known to be an important metabolic pathway for detoxification and elimination of drugs containing aromatic amines. However, the metabolic pathways for piperazine-containing drugs are not fully established. METHODS: N-glucuronidation potential of four piperazine-containing drugs, namely two antihistamines (i.e. cyclizine and chlorcyclizine) and two tetracyclic antidepressants (i.e. mirtazapine and mianserin), was determined by using expressed UDP-glucuronosyltransferase (UGT) enzymes and liver microsomes from both human and animals. RESULTS: Among 13 expressed UGT enzymes, only UGT1A4 and UGT2B10 showed conjugating activities toward these four drugs. Reaction phenotyping, chemical inhibition, and activity correlation analysis revealed that UGT2B10 was a high-affinity enzyme and mainly responsible for hepatic N-glucuronidation of all drugs except mianserin. Both UGT1A4 and UGT2B10 were important contributors to mianserin N-glucuronidation. Moreover, significant species differences were observed in N-glucuronidation of all test drugs. In particular, liver microsomes from four experimental animals (i.e. mouse, rat, dog, and monkey) showed none or negligible activity in catalyzing N-glucuronidation of four drugs. CONCLUSIONS: UGT2B10 plays a critical role in N-glucuronidation of piperazine-containing drugs. Also, conventional experimental animals might be inappropriate models for studying human N-glucuronidation. |
| URL标识 | 查看原文 |
| 语种 | 英语 |
| 源URL | [http://ir.siat.ac.cn:8080/handle/172644/14611]  |
| 专题 | 深圳先进技术研究院_医药所 |
| 推荐引用方式 GB/T 7714 | Danyi Lu,Dong Dong,Baojian Wu. Highly selective N-glucuronidation of four piperazine-containing drugs by UDP-glucuronosyltransferase 2B10[J]. Expert Opinion on Drug Metabolism & Toxicology,2018. |
| APA | Danyi Lu,Dong Dong,&Baojian Wu.(2018).Highly selective N-glucuronidation of four piperazine-containing drugs by UDP-glucuronosyltransferase 2B10.Expert Opinion on Drug Metabolism & Toxicology. |
| MLA | Danyi Lu,et al."Highly selective N-glucuronidation of four piperazine-containing drugs by UDP-glucuronosyltransferase 2B10".Expert Opinion on Drug Metabolism & Toxicology (2018). |
入库方式： OAI收割
来源：深圳先进技术研究院
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。