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This study aimed to assess the catalytic efficiency of 22 CYP3A4 allelic variants on the in\u00a0vitro oxidative metabolism of methadone. We utilized a baculovirus\u2010insect cell expression system to produce recombinant CYP3A4 variants and subsequently assessed their catalytic activity in the <jats:italic>N<\/jats:italic>\u2010demethylation 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.<\/jats:p>","DOI":"10.1002\/bmc.6056","type":"journal-article","created":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T01:36:56Z","timestamp":1733276216000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of CYP3A4 Variants on Methadone Metabolism In\u00a0Vitro"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5763-7174","authenticated-orcid":false,"given":"Chen\u2010chen","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmacy Quzhou KeCheng People's Hospital  Quzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming\u2010lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Quzhou KeCheng People's Hospital  Quzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan\u2010dan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Quzhou KeCheng People's Hospital  Quzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guo\u2010xin","family":"Hu","sequence":"additional","affiliation":[{"name":"Institute of Molecular Toxicology and Pharmacology, School of Pharmaceutical Sciences Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian\u2010ping","family":"Cai","sequence":"additional","affiliation":[{"name":"Institute of Molecular Toxicology and Pharmacology, School of Pharmaceutical Sciences Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"The Key Laboratory of Geriatrics, Beijing Hospital &amp; Beijing Institute of Geriatrics Ministry of Health  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tian","family":"Lan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Quzhou Affiliated Hospital of Wenzhou Medical University Quzhou People's Hospital  Quzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong\u2010feng","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Quzhou Affiliated Hospital of Wenzhou Medical University Quzhou People's Hospital  Quzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,12,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2018.02.020"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.4103\/ijmr.ijmr_1103_22"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742\u20107843.2010.00628.x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.117511"},{"issue":"3","key":"e_1_2_10_6_1","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/S0022-3565(24)29199-0","article-title":"Identification of Variants of CYP3A4 and Characterization of Their Abilities to Metabolize Testosterone and Chlorpyrifos","volume":"299","author":"Dai D.","year":"2001","journal-title":"Journal of Pharmacology and Experimental Therapeutics"},{"issue":"2","key":"e_1_2_10_7_1","first-page":"115","article-title":"Metabolism and Disposition of Prescription Opioids: A Review","volume":"27","author":"DePriest A. 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