Direct and quantitative evaluation of the major human CYP contribution (fmCYP) to drug clearance using the in vitro Silensomes™ model
文献类型：期刊论文
| 作者 | Parmentier, Yannick5; Pothier, Corinne5; Hewitt, Nicola1; Vincent, Ludwig5; Caradec, Fabrice5; Liu, Jia4 ; Lin, Feifei4; Trancart, Marie-Michèle3; Guillet, Fabrice3; Bouaita, Belkacem2
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| 刊名 | Xenobiotica; the fate of foreign compounds in biological systems
 |
| 出版日期 | 2018-01-10 |
| 页码 | 1-14 |
| ISSN号 | 1366-5928 |
| DOI | 10.1080/00498254.2017.1422156 |
| 文献子类 | Article |
| 英文摘要 | 1. We have applied the concept of using MBIs to produce CYP-Silensomes to quantify the contribution of the major CYPs to drug metabolism (fmCYP). 2. The target CYPs were extensively and selectivity inhibited by the selected MBIs, while non-target CYPs were inhibited by less than 20% of the homologous control activities. Only CYP2D6-Silensomes exhibited a CYP2B6 inhibition that could be easily and efficiently encountered by subtracting the fm measured using CYP2B6-Silensomes to adjust the fm. 3. To validate the use of a panel of 6 CYP-Silensomes, we showed that the fmCYP values of mono- and multi-CYP metabolised drugs were well predicted, with 70% within ± 15% accuracy. Moreover, the correlation with observed fmCYP values was higher than that for rhCYPs, which were run in parallel using the same drugs (<45% within ±15% accuracy). Moreover, the choice of the RAF substrate in rhCYP predictions was shown to affect the accuracy of the fmCYP measurement. 4. These results support the use of CYP1A2-, CYP2B6-, CYP2C8-, CYP2C9-, CYP2D6 and CYP3A4-Silensomes to accurately predict fmCYP values during the in vitro enzyme phenotyping assays in early, as well as in development, phases of drug development. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/266254]  |
| 专题 | 上海药物代谢研究中心 |
| 作者单位 | 1.b Scientific Writing Services , Erzhausen , Germany; 2.e Biopredic International , Rennes , France 3.d Eurosafe , Saint-Grégoire , France , and; 4.c SIMM-SERVIER Joint Biopharmacy Laboratory, Shanghai Institute of Materia Medica , Shanghai , China; 5.a Department of Biopharmaceutical Research , Technologie Servier , Orléans Cedex , France; |
| 推荐引用方式 GB/T 7714 | Parmentier, Yannick,Pothier, Corinne,Hewitt, Nicola,et al. Direct and quantitative evaluation of the major human CYP contribution (fmCYP) to drug clearance using the in vitro Silensomes™ model[J]. Xenobiotica; the fate of foreign compounds in biological systems,2018:1-14. |
| APA | Parmentier, Yannick.,Pothier, Corinne.,Hewitt, Nicola.,Vincent, Ludwig.,Caradec, Fabrice.,...&Walther, Bernard.(2018).Direct and quantitative evaluation of the major human CYP contribution (fmCYP) to drug clearance using the in vitro Silensomes™ model.Xenobiotica; the fate of foreign compounds in biological systems,1-14. |
| MLA | Parmentier, Yannick,et al."Direct and quantitative evaluation of the major human CYP contribution (fmCYP) to drug clearance using the in vitro Silensomes™ model".Xenobiotica; the fate of foreign compounds in biological systems (2018):1-14. |
入库方式： OAI收割
来源：上海药物研究所
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