cyp3a4inducerandinhibitorstronglyaffectthepharmacokineticsoftriptolideanditsderivativeinrats
文献类型：期刊论文
| 作者 | Xu Ye; Zhang Yifan ; Chen Xiaoyan; Zhong Dafang
|
| 刊名 | actapharmacologicasinica
 |
| 出版日期 | 2018 |
| 卷号 | 039期号:008页码:1386 |
| 关键词 | 衍生物 老鼠 CYP3a 风湿性关节炎 新陈代谢 相互作用 细胞色素 P450 |
| ISSN号 | 1671-4083 |
| 英文摘要 | Triptolide is the most active ingredient of Tripterygium wilfordfi Hook F, which is used to treat rheumatoid arthritis. （5R）-5- Hydroxytriptolide is a hydroxylation derivative of triptolide with a reduced toxicity. To investigate the metabolic enzymes of the two compounds and the drug-drug interactions with enzyme inducers or inhibitors, a series of in vitro and in vivo experiments were conducted. In vitro studies using recombinant human cytochrome P450 enzyme demonstrated that cytochrome P450 3A4 （CYP3A4） was predominant in the metabolism of triptolide and （5R）-5-hydroxytriptolide, accounting for 94.2% and 64.2% of the metabolism, respectively. Pharmacokinetics studies were conducted in male SD rats following administration of triptolide or （5R）-5-hydroxytriptolide （0.4 mg/kg, po）. The plasma exposure to triptolide and （5R）-5-hydroxytriptolide in the rats was significantly increased when co-administered with the CYP3a inhibitor ritonavir （30 mg/kg, po） with the values of AUC0-∞ （area under the plasma concentration-time curve from time zero extrapolated to infinity） being increased by 6.84 and 1.83 times, respectively. When pretreated with the CYP3a inducer dexamethasone （50 mg.k-1-d-1, for 3 d）, the AUC0-∞ values of triptolide and （5R）-5-hydroxytriptolide were decreased by 85.4% and 91.4%, respectively. These results suggest that both triptoiide and （5R）-5-hydroxytriptolide are sensitive substrates of CYP3a. Because of their narrow therapeutic windows, clinical drug-drug interaction studies should be carried out to ensure their clinical medication safety and efficacy. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/284131]  |
| 专题 | 中国科学院上海药物研究所 |
| 作者单位 | 中国科学院上海药物研究所 |
| 推荐引用方式 GB/T 7714 | Xu Ye,Zhang Yifan,Chen Xiaoyan,et al. cyp3a4inducerandinhibitorstronglyaffectthepharmacokineticsoftriptolideanditsderivativeinrats[J]. actapharmacologicasinica,2018,039(008):1386. |
| APA | Xu Ye,Zhang Yifan,Chen Xiaoyan,&Zhong Dafang.(2018).cyp3a4inducerandinhibitorstronglyaffectthepharmacokineticsoftriptolideanditsderivativeinrats.actapharmacologicasinica,039(008),1386. |
| MLA | Xu Ye,et al."cyp3a4inducerandinhibitorstronglyaffectthepharmacokineticsoftriptolideanditsderivativeinrats".actapharmacologicasinica 039.008(2018):1386. |
入库方式： OAI收割
来源：上海药物研究所
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。