题名 | The impacts of natural product miltirone and the CYP2D6 pharmacogenetic phenotype on fluoxetine metabolism |
作者 | |
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, CYP2D6*92 and CYP2D6*96/Q424X were found to be catalytically inactive for fluoxetine metabolism, five variants (CYP2D6*89/L142S, *97/F457L, *R497, *V342M and *R344Q) exhibited markedly increased clearance values (>125.07%) and seven variants (CYP2D6*2, *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). |
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