A A Skryabina, V V Nikiforov, M Z Shakhmardanov, M S Zastrozhin, D A Sychev
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引用次数: 0
摘要
背景：大环内酯类药物是广泛使用的抗生素，但药物不良反应（adr），特别是在遗传易感个体，可危及其安全性。本研究探讨了药理学标记物对流感细菌性并发症患者大环内酯安全性的影响。目的：探讨大环内酯类药物治疗过程中转运蛋白（ABCB1）和酶（CYP3A4、CYP3A5）基因多态性对不良反应风险的影响。方法：一项前瞻性研究纳入了100名接受阿奇霉素或红霉素治疗5天的流感下呼吸道细菌并发症的参与者。基因分型针对ABCB1 （3435C>T）、CYP3A4 （C>T内含子6）和CYP3A5 （6986A>G）多态性。每天监测不良反应并与遗传标记相关。结果：ABCB1 （3435C>T）多态性与CT和TT基因型中腹痛和腹泻发生率升高相关（OR = 2.12, p = 0.043）。CYP3A4 （C>T内含子6）多态性增加了红霉素治疗参与者的不良反应风险（OR = 24.0, p = 0.0339）。CYP3A5 （6986A>G）未见明显影响。结论：ABCB1和CYP3A4基因的遗传多态性可预测大环内酯类药物相关的不良反应。药物遗传学筛查可以提高大环内酯类药物的安全性，特别是对遗传易感个体。
Pharmacogenetic markers and macrolide safety in influenza patients: insights from a prospective study.
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.
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