题名 | Effect of flavonoids and CYP3A4 variants on midostaurin metabolism |
作者 | |
发表日期 | 2023-04 |
发表期刊 | Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 影响因子和分区 |
语种 | 英语 |
原始文献类型 | Journal Article |
关键词 | CYP3A4 Flavonoids Genetic polymorphism Interaction Midostaurin Myricetin |
其他关键词 | ACUTE MYELOID-LEUKEMIA ; GENETIC POLYMORPHISMS ; IN-VIVO ; PHARMACOKINETICS ; ANTIBACTERIAL ; INHIBITION ; MYRICETIN ; APIGENIN |
摘要 | The objective of this study was to determine the effect of flavonoids on midostaurin disposition considering co-administration and metabolic enzyme gene polymorphism. Enzymatic incubation assays were performed in vitro, while in vivo experiments were conducted in Sprague-Dawley rats. The analytes were determined via UPLC-MS/MS. We found that myricetin was the most potent among the investigated 10 flavonoids in suppressing the metabolism of midostaurin, with an IC50 at a low μM level. After co-administration of midostaurin and myricetin, the plasma concentration of midostaurin's primary metabolite CGP62221 was reduced corresponding to myricetin exposure. Furthermore, CYP3A4 homologous rat protein CYP3A2 was reduced significantly in the co-administration group. Thereafter, the kinetic parameters of 23 recombinant human CYP3A4 variants were determined using midostaurin. The relative intrinsic clearance varied from 269.63% in CYP3A4.29-8.95% in CYP3A4.17. In addition, the inhibitory potency of myricetin was substantially different for CYP3A4.29 and CYP3A4.17 compared with wild type, with IC50 values of 9.85 ± 0.27 μM and 90.99 ± 16.13 μM, respectively. Collectively, our data demonstrated that flavonoids, particularly myricetin, can inhibit the metabolism of midostaurin. Additionally, CYP3A4 genetic polymorphism may contribute to stratification of midostaurin blood exposure |
资助项目 | National Key Research and Development Program of China [2020YFC2008301] ; National Natural Science Foundation of China [81973397] ; Natural ScienceFoundation of Zhejiang Province [LTGC23H310001] |
出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
ISSN | 0278-6915 |
EISSN | 1873-6351 |
卷号 | 174 |
DOI | 10.1016/j.fct.2023.113669 |
页数 | 10 |
WOS类目 | Food Science & Technology ; Toxicology |
WOS研究方向 | Food Science & Technology ; Toxicology |
WOS记录号 | WOS:000946794700001 |
收录类别 | SCIE ; PUBMED ; SCOPUS |
在线发表日期 | 2023-02 |
URL | 查看原文 |
PubMed ID | 36805545 |
SCOPUSEID | 2-s2.0-85148670253 |
通讯作者地址 | [Hu, Guo-xin]School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,325035,China ; [Qian, Jian-chang]School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,325035,China |
Scopus学科分类 | Food Science;Toxicology |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | https://kms.wmu.edu.cn/handle/3ETUA0LF/172788 |
专题 | 附属第一医院 药学院(分析测试中心) 药学院(分析测试中心)_分子药理研究与教学中心 |
通讯作者 | Hu, Guo-xin; Qian, Jian-chang |
作者单位 | 1.The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China; 2.Institute of Molecular Toxicology and Pharmacology,School of Pharmaceutical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,China |
第一作者单位 | 附属第一医院; 第一临床医学院(信息与工程学院)、附属第一医院; 药学院(分析测试中心) |
通讯作者单位 | 药学院(分析测试中心) |
第一作者的第一单位 | 附属第一医院 |
推荐引用方式 GB/T 7714 | Xu, Ren-ai,Li, Qing-qing,Gao, Nan-yong,et al. Effect of flavonoids and CYP3A4 variants on midostaurin metabolism[J]. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association,2023,174. |
APA | Xu, Ren-ai., Li, Qing-qing., Gao, Nan-yong., Wang, Jing., Li, Xin-yue., ... & Qian, Jian-chang. (2023). Effect of flavonoids and CYP3A4 variants on midostaurin metabolism. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 174. |
MLA | Xu, Ren-ai,et al."Effect of flavonoids and CYP3A4 variants on midostaurin metabolism".Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 174(2023). |
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