| アブストラクト | Background: Antiviral therapies are widely used during pregnancy and are generally considered safe, pregnancy-specific severe safety signals continue to be observed in post-marketing pharmacovigilance data. These signals are rarely interpreted within an integrated mechanistic framework. Methods: We analysed pregnancy-related EudraVigilance reports (2015-2025) using a previously network-based pharmacovigilance framework. Established ADR clusters were treated as fixed phenotypes and integrated with in silico ADMET liabilities, literature-derived pregnancy pharmacokinetic/pharmacodynamic (PK/PD) parameters, polypharmacy and co-medication network metrics, and exploratory statistical, machine-learning, and exposure-liability analyses for mechanistic prioritisation. Results: Phenotype membership explained 22.3% of the variance in composite ADMET risk (intraclass correlation coefficient = 0.223; p < 0.001), and all tested ADMET parameters differed significantly across phenotypes (FDR-adjusted p < 10(-10)). One phenotype showed pronounced enrichment, with 13 antivirals over-represented. Polypharmacy strongly modified seriousness, with odds of serious outcomes increasing by ~5% per additional co-reported active drug (OR 1.05, 95% CI 1.04-1.05). A composite mechanistic vulnerability index showed moderate concordance with empirical burden (Spearman's rho = 0.65), while regimen-level prioritisation of drug-drug interactions (DDIs) identified no high-priority combinations. Conclusions: Pregnancy-related antiviral ADRs cluster into reproducible phenotypes driven by mechanistic liability and system-level complexity, supporting mechanistically informed prioritisation and targeted pharmacometric follow-up. |
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| ジャーナル名 | Pharmaceuticals (Basel, Switzerland) |
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| Pubmed追加日 | 2026/3/28 |
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| 投稿者 | Costa, Barbara; Vale, Nuno |
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| 組織名 | PerMed Research Group, RISE-Health, Faculty of Medicine, University of Porto,;Alameda Professor Hernani Monteiro, 4200-319 Porto, Portugal.;RISE-Health, Department of Community Medicine, Health Information and Decision;(MEDCIDS), Faculty of Medicine, University of Porto, Rua Doutor Placido da Costa,;4200-450 Porto, Portugal.;Laboratory of Personalized Medicine, Department of Community Medicine, Health;Information and Decision (MEDCIDS), Faculty of Medicine, University of Porto, Rua;Doutor Placido da Costa, 4200-450 Porto, Portugal. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/41901296/ |
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