The effect of CYP3A4 genetic polymorphism and drug interaction on the metabolism of istradefylline

Hu, Xiaoqin; Ni, Jin-Huan; Gao, Nanyong; Ye, Zhize; Hu, Guoxin; Cai, Jianping; Qian, Jian-chang

doi:10.1016/j.cbi.2022.110123

Cited by 6 publications

(2 citation statements)

References 27 publications

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“…These core pharmacological proteins included CYP3A4 , and NOS2 . CYP3A4, mainly occurs in the liver and gut, is involved in the metabolism of drugs [ 40 ]. It is reported that hepatic drug-metabolizing enzymes, such as CYP3A4, can catalyze the biotransformation of APAP for biological detoxification [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics approach and experimental validation reveal the hepatoprotective effect of pachyman against acetaminophen-associated liver injury

Wu,

Qin,

Liu

et al. 2023

Aging

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Pachyman, known as Poria cocos polysaccharides, refers to the bioactive compounds isolated from Poria cocos . Pachyman is thought to exert cytoprotective action. However, the detailed mechanisms of pachyman action for hepatoprotection remain unknown. In this study, we aimed to assess the therapeutic actions, molecular mechanisms, and key target proteins of pachyman in the treatment of liver injury through network pharmacology and molecular docking assays. Furthermore, these bioinformatic findings were validated by an acetaminophen (APAP)-induced liver injury in vivo . Primarily using bioinformatic analysis, we screened and characterized 12 genes that act as potential therapeutic targets of pachyman against APAP-induced liver injury, in which all core targets were obtained. By using enrichment analysis, these core target genes of pachyman were characterized to reveal the pharmacological functions and molecular mechanisms of anti-liver injury induced by APAP. A molecular docking simulation was further performed to certain anti-liver injury target proteins of pachyman, including cytochrome P450 3A4 enzyme ( CYP3A4 ) and inducible nitric oxide synthase (NOS2) . In animal experiments, pachyman exerted potent hepatoprotective activities in prenatal APAP-exposed offspring livers, characterized by activated hepatocellular CYP3A4 and NOS2 expressions. These current findings have thus indicated that pachyman exerts hepatoprotective effects and may be the promising nutraceuticals for the treatment of APAP-induced liver injury.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics approach and experimental validation reveal the hepatoprotective effect of pachyman against acetaminophen-associated liver injury

Wu,

Qin,

Liu

et al. 2023

Aging

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“…Similar to previous reports, the relative clearance of most CYP3A4 variants decreased significantly compared with the wild type (Yuan et al, 2023). In particular, CYP3A4.12, 13, 17, and 20 lost almost all enzymatic function (Han et al, 2021;Hu et al, 2022). Patients who carry these alleles are deficient in CYP3A4 activity.…”

Section: Discussionmentioning

confidence: 99%

Gene Polymorphisms and Drug–Drug Interactions Determine the Metabolic Profile of Blonanserin

Ye,

Li,

et al. 2023

J Pharmacol Exp Ther

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This study aimed to evaluate the effects of cytochrome P450 3A4 (CYP3A4) gene polymorphism and drug interaction on the metabolism of blonanserin. Human recombinant CYP3A4 was prepared using the Bac-to-Bac baculovirus expression system. A microsomal enzyme reaction system was established, and drug-drug interactions were evaluated using Sprague-Dawley rats.Ultra-performance liquid chromatography-tandem mass spectrometry was used to detect the concentrations of blonanserin and its metabolite. Compared with wild-type CYP34A, the relative clearance of blonanserin by CYP3A4.29 significantly increased to 251.3%, while it decreased

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Advancing personalized medicine in neurodegenerative diseases: The role of epigenetics and pharmacoepigenomics in pharmacotherapy

Griñán-Ferré,

Bellver-Sanchis,

Guerrero

et al. 2024

Pharmacological Research

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The effect of CYP3A4 genetic polymorphism and drug interaction on the metabolism of istradefylline

Cited by 6 publications

References 27 publications

Bioinformatics approach and experimental validation reveal the hepatoprotective effect of pachyman against acetaminophen-associated liver injury

Bioinformatics approach and experimental validation reveal the hepatoprotective effect of pachyman against acetaminophen-associated liver injury

Gene Polymorphisms and Drug–Drug Interactions Determine the Metabolic Profile of Blonanserin

Advancing personalized medicine in neurodegenerative diseases: The role of epigenetics and pharmacoepigenomics in pharmacotherapy

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