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

• DOI: 10.3389/fphar.2024.1373048
• Publication Date: 2024-04-29T04:38:12Z
• Authors: Xiaodan Zhang; Qingqing Li; Xinwu Ye; Qing Chen; Chen Chen; Guoxin Hu; Likang Zhang; Lianguo Chen
• Keywords: Natural product

Introduction: To study the effects of drug-induced CYP2D6 activity inhibition and genetic polymorphisms on fluoxetine metabolism, rat liver microsomes (RLMs) SD rats were used to investigate potential drug‒drug interactions (DDIs), http://muchong.com/t-10728934-1 recombinant baculosomes prepared subjected catalytic reactivity studies. Methods Results: All analytes 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 metabolism in RLMs. In vivo , concentration blood increased markedly after administration. The molecular docking results showed that bound more strongly than fluoxetine, PHE120 may be key residue leading CYP2D6-mediated N-demethylation miltirone. terms polymorphism intrinsic clearance values most variants significantly altered. Among these variants, CYP2D6*92 CYP2D6*96/Q424X found catalytically inactive five (CYP2D6*89/L142S, *97/F457L, *R497, *V342M *R344Q) exhibited (>125.07%) seven (CYP2D6*2, *10, *87/A5V, *93/T249P, *E215K, *R25Q *R440C) decreased (from 6.62% 66.79%) compared those wild-type. Conclusion: Our suggest attention should given subjects clinic who take also carry one infrequent alleles or are coadministered drugs containing