Effects of three flavonoids on the metabolism of lenvatinib

doi:10.3389/fphar.2024.1438259

科研成果详情

题名	Effects of three flavonoids on the metabolism of lenvatinib
作者	Yang, Jinzhao 1; Chen, Jie 2; Li, Qingqing 2; Xu, Ren-ai2; Chen, Xiaohai 3
发表日期	2024-08-20
发表期刊	FRONTIERS IN PHARMACOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	hepatocellular carcinoma lenvatinib flavonoids luteolin DDIs
其他关键词	UNRESECTABLE HEPATOCELLULAR-CARCINOMA ; DRUG-DRUG INTERACTIONS ; IN-VITRO ; 1ST-LINE TREATMENT ; KINASE INHIBITOR ; NON-INFERIORITY ; PHARMACOKINETICS ; MYRICETIN ; MANAGEMENT ; SUPPRESSES
摘要	Lenvatinib is a first-line therapy for the treatment of hepatocellular carcinoma (HCC), an active multi-target tyrosine kinase inhibitor (TKI). The interaction between Traditional Chinese Medicine (TCM) and chemicals has increasingly become a research hotspot. The objective of this study was to pinpoint the effects of three flavonoids on the metabolism of lenvatinib. Enzyme reaction system was established and optimized in vitro, and in vivo experiments were conducted in Sprague-Dawley (SD) rats, where the analytes were detected by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). We found that among three flavonoids, luteolin and myricetin had strong inhibitory effects on lenvatinib metabolism, with half-maximal inhibitory concentration (IC50) values of 11.36 +/- 0.46 mu M and 11.21 +/- 0.81 mu M in rat liver microsomes (RLM), respectively, and 6.89 +/- 0.43 mu M and 12.32 +/- 1.21 mu M in human liver microsomes (HLM), respectively. In Sprague-Dawley rats, the combined administration of lenvatinib and luteolin obviously expanded the exposure to lenvatinib; however, co-administered with myricetin did not have any changes, which may be due to the poor bioavailability of myricetin in vivo. Furthermore, the inhibitory type of luteolin on lenvatinib showed an un-competitive in RLM and a mixed in HLM. Collectively, flavonoids with liver protection, especially luteolin, may inhibit lenvatinib metabolism in vitro and in vivo.
出版者	FRONTIERS MEDIA SA
EISSN	1663-9812
卷号	15
DOI	10.3389/fphar.2024.1438259
页数	10
WOS类目	Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:001302716500001
收录类别	SCIE
PubMed ID	39228528
通讯作者地址	[Xu, Ren-ai]Wenzhou Med Univ, Affiliated Hosp 1, Wenzhou, Zhejiang, Peoples R China. ; [Chen, Xiaohai]Wenzhou Med Univ, Affiliated Hosp 3, Wenzhou, Zhejiang, Peoples R China.
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/218743
专题	附属第一医院其他_温州市第三临床学院（温州市人民医院）其他_附属第三医院（瑞安市人民医院）
通讯作者	Xu, Ren-ai; Chen, Xiaohai
作者单位	1.Wenzhou Med Univ, Wenzhou Peoples Hosp, Clin Inst 3, Wenzhou, Zhejiang, Peoples R China; 2.Wenzhou Med Univ, Affiliated Hosp 1, Wenzhou, Zhejiang, Peoples R China; 3.Wenzhou Med Univ, Affiliated Hosp 3, Wenzhou, Zhejiang, Peoples R China
第一作者单位	温州医科大学
通讯作者单位	附属第一医院; 附属第三医院（瑞安市人民医院）; 温州市第三临床学院（温州市人民医院）
第一作者的第一单位	温州医科大学
推荐引用方式 GB/T 7714	Yang, Jinzhao,Chen, Jie,Li, Qingqing,et al. Effects of three flavonoids on the metabolism of lenvatinib[J]. FRONTIERS IN PHARMACOLOGY,2024,15.
APA	Yang, Jinzhao, Chen, Jie, Li, Qingqing, Xu, Ren-ai, & Chen, Xiaohai. (2024). Effects of three flavonoids on the metabolism of lenvatinib. FRONTIERS IN PHARMACOLOGY, 15.
MLA	Yang, Jinzhao,et al."Effects of three flavonoids on the metabolism of lenvatinib".FRONTIERS IN PHARMACOLOGY 15(2024).