The impacts of natural product miltirone and the CYP2D6 pharmacogenetic phenotype on fluoxetine metabolism

doi:10.3389/fphar.2024.1373048

科研成果详情

题名	The impacts of natural product miltirone and the CYP2D6 pharmacogenetic phenotype on fluoxetine metabolism
作者	Zhang, Xiaodan 1,2; Li, Qingqing 2,3; Ye, Xinwu 1; Chen, Qing 2; Chen, Chen2; Hu, Guoxin3; Zhang, Likang3; Chen, Lianguo2
发表日期	2024-04-29
发表期刊	Frontiers in pharmacology 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	CYP2D6 variants drug‒drug interaction fluoxetine miltirone norfluoxetine
其他关键词	N-DEMETHYLATION ; GENETIC POLYMORPHISMS ; SALVIA-MILTIORRHIZA ; CHINESE POPULATION ; VARIANTS ; NORFLUOXETINE ; CHILD
摘要	Introduction: To study the effects of drug-induced CYP2D6 activity inhibition and genetic polymorphisms on fluoxetine metabolism, rat liver microsomes (RLMs) and SD rats were used to investigate the potential drug‒drug interactions (DDIs), and CYP2D6 http://muchong.com/t-10728934-1 recombinant baculosomes were prepared and subjected to catalytic reactivity studies. Methods and Results: All analytes were detected by ultraperformance liquid chromatography-tandem mass spectrometry (UPLC‒MS/MS). After screening for 27 targeted natural products, miltirone was identified as having obvious inhibitory effect on fluoxetine metabolism in RLMs. In vivo, the concentration of fluoxetine in rat blood increased markedly after miltirone administration. The molecular docking results showed that miltirone bound more strongly to CYP2D6 than fluoxetine, and PHE120 may be the key residue leading to the inhibition of CYP2D6-mediated fluoxetine N-demethylation by miltirone. In terms of the genetic polymorphism of CYP2D6 on fluoxetine metabolism, the intrinsic clearance values of most variants were significantly altered. Among these variants, CYP2D692 and CYP2D696/Q424X were found to be catalytically inactive for fluoxetine metabolism, five variants (CYP2D689/L142S, 97/F457L, R497, V342M and R344Q) exhibited markedly increased clearance values (>125.07%) and seven variants (CYP2D62, 10, 87/A5V, 93/T249P, E215K, R25Q and R440C) exhibited significantly decreased clearance values (from 6.62% to 66.79%) compared to those of the wild-type. Conclusion: Our results suggest that more attention should be given to subjects in the clinic who take fluoxetine and also carry one of these infrequent CYP2D6 alleles or are coadministered drugs containing miltirone
资助项目	Wenzhou City Public Welfare project from LC [Y20220903]; Medical and Health Science and Technology Project of Zhejiang Provincial Health Commission [2022RC072]
出版者	FRONTIERS MEDIA SA
ISSN	1663-9812
EISSN	1663-9812
卷号	15
DOI	10.3389/fphar.2024.1373048
页数	12
WOS类目	Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:001219724200001
收录类别	PUBMED ; SCIE ; SCOPUS
URL	查看原文
PubMed ID	38741591
SCOPUSEID	2-s2.0-85193003513
通讯作者地址	[Chen, Lianguo]Department of Clinical Pharmacy,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,China ; [Zhang, Likang]Renji College,Wenzhou Medical University,Zhejiang,Wenzhou,China
Scopus学科分类	Pharmacology;Pharmacology (medical)
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/212869
专题	附属第一医院仁济学院
通讯作者	Zhang, Likang; Chen, Lianguo
作者单位	1.Wenzhou, Wenzhou, Zhejiang, China; 2.Department of Clinical Pharmacy,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,China; 3.Renji College,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
通讯作者单位	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; 仁济学院
推荐引用方式 GB/T 7714	Zhang, Xiaodan,Li, Qingqing,Ye, Xinwu,et al. The impacts of natural product miltirone and the CYP2D6 pharmacogenetic phenotype on fluoxetine metabolism[J]. Frontiers in pharmacology,2024,15.
APA	Zhang, Xiaodan., Li, Qingqing., Ye, Xinwu., Chen, Qing., Chen, Chen., ... & Chen, Lianguo. (2024). The impacts of natural product miltirone and the CYP2D6 pharmacogenetic phenotype on fluoxetine metabolism. Frontiers in pharmacology, 15.
MLA	Zhang, Xiaodan,et al."The impacts of natural product miltirone and the CYP2D6 pharmacogenetic phenotype on fluoxetine metabolism".Frontiers in pharmacology 15(2024).