A A Skryabina, V V Nikiforov, M Z Shakhmardanov, M S Zastrozhin, D A Sychev
{"title":"Pharmacogenetic markers and macrolide safety in influenza patients: insights from a prospective study.","authors":"A A Skryabina, V V Nikiforov, M Z Shakhmardanov, M S Zastrozhin, D A Sychev","doi":"10.1080/14622416.2025.2454217","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Macrolides are widely used antibiotics, but adverse drug reactions (ADRs), particularly in genetically predisposed individuals, can compromise their safety. This study examines the impact of pharmacogenetic markers on macrolide safety in participants with bacterial complications of influenza.</p><p><strong>Objective: </strong>To evaluate how polymorphisms in genes encoding transporter proteins (ABCB1) and enzymes (CYP3A4, CYP3A5) influence ADR risk during macrolide therapy.</p><p><strong>Methods: </strong>A prospective study included 100 participants with lower respiratory tract bacterial complications of influenza treated with azithromycin or erythromycin for five days. Genotyping targeted <i>ABCB1 (3435C>T)</i>, <i>CYP3A4 (C>T intron 6)</i>, and <i>CYP3A5 (6986A>G)</i> polymorphisms. ADRs were monitored daily and correlated with genetic markers.</p><p><strong>Results: </strong>The <i>ABCB1 (3435C>T)</i> polymorphism was associated with higher rates of abdominal pain and diarrhea in <i>CT</i> and <i>TT</i> genotypes (OR = 2.12, <i>p</i> = 0.043). The <i>CYP3A4 (C>T intron 6)</i> polymorphism increased ADR risk in erythromycin-treated participants (OR = 24.0, <i>p</i> = 0.0339). No significant effects were observed for <i>CYP3A5 (6986A>G).</i></p><p><strong>Conclusion: </strong>Genetic polymorphisms in <i>ABCB1</i> and <i>CYP3A4</i> genes predict macrolide-related ADRs. Pharmacogenetic screening could improve macrolide safety, particularly for genetically susceptible individuals.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"1-5"},"PeriodicalIF":1.9000,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacogenomics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/14622416.2025.2454217","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Macrolides are widely used antibiotics, but adverse drug reactions (ADRs), particularly in genetically predisposed individuals, can compromise their safety. This study examines the impact of pharmacogenetic markers on macrolide safety in participants with bacterial complications of influenza.
Objective: To evaluate how polymorphisms in genes encoding transporter proteins (ABCB1) and enzymes (CYP3A4, CYP3A5) influence ADR risk during macrolide therapy.
Methods: A prospective study included 100 participants with lower respiratory tract bacterial complications of influenza treated with azithromycin or erythromycin for five days. Genotyping targeted ABCB1 (3435C>T), CYP3A4 (C>T intron 6), and CYP3A5 (6986A>G) polymorphisms. ADRs were monitored daily and correlated with genetic markers.
Results: The ABCB1 (3435C>T) polymorphism was associated with higher rates of abdominal pain and diarrhea in CT and TT genotypes (OR = 2.12, p = 0.043). The CYP3A4 (C>T intron 6) polymorphism increased ADR risk in erythromycin-treated participants (OR = 24.0, p = 0.0339). No significant effects were observed for CYP3A5 (6986A>G).
Conclusion: Genetic polymorphisms in ABCB1 and CYP3A4 genes predict macrolide-related ADRs. Pharmacogenetic screening could improve macrolide safety, particularly for genetically susceptible individuals.
期刊介绍:
Pharmacogenomics (ISSN 1462-2416) is a peer-reviewed journal presenting reviews and reports by the researchers and decision-makers closely involved in this rapidly developing area. Key objectives are to provide the community with an essential resource for keeping abreast of the latest developments in all areas of this exciting field.
Pharmacogenomics is the leading source of commentary and analysis, bringing you the highest quality expert analyses from corporate and academic opinion leaders in the field.