| アブストラクト | OBJECTIVE: The comprehensive safety profile and underlying molecular mechanisms of ivermectin-associated adverse drug reactions (ADRs) remain to be fully elucidated. METHODS: We integrated pharmacovigilance data from the FDA Adverse Event Reporting System (FAERS) with network toxicology and transcriptomic validation. Disproportionality analyses were conducted on 1,421 ivermectin-related reports to detect signals at the System Organ Class (SOC) and Preferred Term (PT) levels. Network-based approaches, including protein-protein interaction (PPI) analysis and molecular docking, were employed to identify core toxicity targets, followed by ADMET property prediction. RESULTS: Significant safety signals emerged for Eye disorders, Nervous system disorders, and General disorders. Frequently reported PTs included asthenia, headache, and pyrexia, alongside notable serious signals such as encephalopathy (ROR = 24.1) and toxic encephalopathy (ROR = 16.18). Network toxicology identified five core targets shared across key SOCs: EGFR, ERBB2, TGFB1, PIK3CA, and HSPG2. KEGG enrichment analysis highlighted pathways related to parasitic diseases, leukocyte migration, and endocrine regulation. Molecular docking confirmed high binding affinity between ivermectin components and EGFR (</= -8.7 kcal/mol). ADMET predictions indicated elevated risks for genotoxicity, ototoxicity, and skin sensitization. CONCLUSION: Ivermectin-associated ADRs manifest across multiple organ systems, which are potentially associated with the modulation of predicted candidate targets including EGFR, ERBB2, TGFB1, PIK3CA, and HSPG2. |
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| ジャーナル名 | Frontiers in cellular and infection microbiology |
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| Pubmed追加日 | 2026/9/10 |
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| 投稿者 | Liu, Boyi; Chen, Xiaoze; Wang, Yishuo; Zhang, Hao; Liang, Xiao; Guan, Xin; Zhang, Wenchao; Han, Ao; Chen, Danna |
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| 組織名 | The First Clinical College, Changsha Medical University, Changsha, China.;College of Basic Medical Sciences, Naval Medical University, Shanghai, China.;Department of Nuclear Medicine, First Hospital of Shanxi Medical University,;Shanxi Medical University, Taiyuan, Shanxi, China.;Department of Basic Medical Sciences, Changsha Medical University, Changsha,;Hunan, China.;Hunan Provincial University Key Laboratory of the Fundamental and Clinical;Research on Functional Nucleic Acid, Changsha Medical University,;Changsha, China. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/42718790/ |
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