科研成果详情

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
ISSN0278-6915
EISSN1873-6351
卷号174
DOI10.1016/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 ID36805545
SCOPUSEID2-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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