Functional evaluation of CYP2C19 and CYP3A4 gene polymorphism on ibuprofen metabolism

Yuan, Ling-jing; Li, Xiangyu; Ni, Jin-Huan; Wang, Jing; Xu, Xiaoyu; Luo, Jing; Zhou, Qi Tony; Hu, Guoxin; Cai, Jianping; Qian, Jianchang

doi:10.1016/j.taap.2023.116653

Toxicology and Applied Pharmacology

2023

DOI: 10.1016/j.taap.2023.116653

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Functional evaluation of CYP2C19 and CYP3A4 gene polymorphism on ibuprofen metabolism

Ling-jing Yuan

Xiangyu Li

Jin-Huan Ni

et al.

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Cited by 2 publications

References 37 publications

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Effects of CYP3A4 Variants on Methadone Metabolism In Vitro

Wang,

Zhang,

et al. 2024

Biomedical Chromatography

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In hepatic drug metabolism, cytochrome P450 (CYP450) enzymes, particularly CYP3A4, catalyze the majority of drug biotransformations, accounting for over 50% of the CYP450 family's metabolic capacity. This study aimed to assess the catalytic efficiency of 22 CYP3A4 allelic variants on the in vitro oxidative metabolism of methadone. We utilized a baculovirus‐insect cell expression system to produce recombinant CYP3A4 variants and subsequently assessed their catalytic activity in the N‐demethylation of methadone. Of the 23 tested CYP3A4 allelic variants, CYP3A4*1 represents the wild type. Compared with CYP3A4*1, 12 variants displayed significantly lower intrinsic clearance of methadone, while 3 variants showed increased intrinsic clearance of methadone. Additionally, six variants demonstrated no significant difference in intrinsic clearance of methadone compared to CYP3A4*1, and one variant showed no detectable expression. Our evaluation of the enzymatic activity of CYP3A4 gene polymorphisms on methadone can aid in the personalized clinical use of methadone and facilitate the investigation into the relationship between genetic variations and clinical phenotypes.

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Effects of CYP3A4 Variants on Methadone Metabolism In Vitro

Wang,

Zhang,

et al. 2024

Biomedical Chromatography

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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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Functional evaluation of CYP2C19 and CYP3A4 gene polymorphism on ibuprofen metabolism

Cited by 2 publications

References 37 publications

Effects of CYP3A4 Variants on Methadone Metabolism In Vitro

Effects of CYP3A4 Variants on Methadone Metabolism In Vitro

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

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