Inhibitory effect of imperatorin on dabrafenib metabolism in vitro and in vivo

doi:10.1016/j.cbi.2024.111131

科研成果详情

题名	Inhibitory effect of imperatorin on dabrafenib metabolism in vitro and in vivo
作者	Xia, Hailun1; Wu, Hualu2; Chen, Jie 1; Xu, Xinhao1; Tan, Wei 3; Xu, Ren-ai 1,2
发表日期	2024-08-25
发表期刊	Chemico-biological interactions 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	Dabrafenib Drug-drug interaction Imperatorin Pharmacokinetic
其他关键词	PHARMACOKINETICS ; ETHNOPHARMACOLOGY ; PHYTOCHEMISTRY ; PROFILE ; CELLS
摘要	Dabrafenib is a BRAF inhibitor that has been demonstrated to be efficacious in the treatment of melanoma and non-small-cell lung cancer patients with BRAF V600E mutations. The objective of this study was to investigate the effects of 51 traditional Chinese medicines on the metabolism of dabrafenib and to further investigate the inhibitory effect of imperatorin. The quantification of dabrafenib and its metabolite hydroxy-dabrafenib was carried out using a sensitive, rapid, and accurate assay method based on ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The results of in vitro experiments showed that 20 drugs inhibited the metabolism of dabrafenib by more than 80 %. In a further study of imperatorin on dabrafenib, the half-maximal inhibitory concentration (IC50) values of imperatorin on dabrafenib were 0.22 μM and 3.68 μM in rat liver microsomes (RLM) and human liver microsomes (HLM), respectively, while the inhibition mechanisms were non-competitive and mixed type inhibition, respectively. The results of in vivo experiments demonstrated that in the presence of imperatorin, the AUC(0-t), AUC(0-∞), Cmax, and Tmax of dabrafenib were increased by 2.38-, 2.26-, 1.05-, and 6.10-fold, respectively, while CLz/F was decreased by 67.9 %. In addition, Tmax of hydroxy-dabrafenib was increased by 1.4-fold. The results of the research showed that imperatorin had a consistent inhibitory effect on dabrafenib in vitro and in vivo. When the concurrent use of dabrafenib and imperatorin is unavoidable, clinicians should closely monitor for potential adverse events and make timely adjustments to the administered dosage
资助项目	National Natural Science Foundation of China [82104297, WYYY-IACUC-AEC-2024-020]
出版者	ELSEVIER IRELAND LTD
ISSN	0009-2797
EISSN	1872-7786
卷号	399
DOI	10.1016/j.cbi.2024.111131
页数	10
WOS类目	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Toxicology
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Toxicology
WOS记录号	WOS:001270677200001
收录类别	PUBMED ; SCIE ; SCOPUS
URL	查看原文
PubMed ID	38964639
SCOPUSEID	2-s2.0-85197477482
通讯作者地址	[Xu, Ren-ai]Wenzhou Med Univ, Dept Pharm, Affiliated Hosp 1, Wenzhou, Zhejiang, Peoples R China. ; [Tan, Wei]Chongqing Med Univ, Affiliated Hosp 3, Gener Hosp, Chongqing, Peoples R China.
Scopus学科分类	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/215695
专题	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_药学部
通讯作者	Tan, Wei; Xu, Ren-ai
作者单位	1.Wenzhou Med Univ, Dept Pharm, Affiliated Hosp 1, Wenzhou, Zhejiang, Peoples R China; 2.Wenzhou Med Univ, Affiliated Hosp 1, Key Lab Diag & Treatment Severe Hepatopancreat Dis, Wenzhou, Zhejiang, Peoples R China; 3.Chongqing Med Univ, Affiliated Hosp 3, Gener Hosp, Chongqing, Peoples R China
第一作者单位	第一临床医学院（信息与工程学院）、附属第一医院_药学部
通讯作者单位	第一临床医学院（信息与工程学院）、附属第一医院_药学部
第一作者的第一单位	第一临床医学院（信息与工程学院）、附属第一医院_药学部
推荐引用方式 GB/T 7714	Xia, Hailun,Wu, Hualu,Chen, Jie,et al. Inhibitory effect of imperatorin on dabrafenib metabolism in vitro and in vivo[J]. Chemico-biological interactions,2024,399.
APA	Xia, Hailun, Wu, Hualu, Chen, Jie, Xu, Xinhao, Tan, Wei, & Xu, Ren-ai. (2024). Inhibitory effect of imperatorin on dabrafenib metabolism in vitro and in vivo. Chemico-biological interactions, 399.
MLA	Xia, Hailun,et al."Inhibitory effect of imperatorin on dabrafenib metabolism in vitro and in vivo".Chemico-biological interactions 399(2024).