Ida M Heerfordt, Ditte Resendal Gotfredsen, Henrik Horwitz, Anette Kirstine Stark, Jon Trærup Andersen, Christina Gade, Ulrik Lausten-Thomsen, Rasmus Huan Olsen
{"title":"EudraVigilance insights: Suspected adverse drug reactions in infants through breastfeeding.","authors":"Ida M Heerfordt, Ditte Resendal Gotfredsen, Henrik Horwitz, Anette Kirstine Stark, Jon Trærup Andersen, Christina Gade, Ulrik Lausten-Thomsen, Rasmus Huan Olsen","doi":"10.1002/bcp.70063","DOIUrl":"https://doi.org/10.1002/bcp.70063","url":null,"abstract":"<p><strong>Aims: </strong>We aimed to describe suspected adverse drug reactions (ADRs) in infants resulting from medications transmitted through mothers' milk, as reported to the European ADR database, EudraVigilance. The research sought to understand the frequency, seriousness and nature of these ADRs to assess potential risks associated with maternal medication use during breastfeeding.</p><p><strong>Methods: </strong>Data from EudraVigilance were analysed. The study included all reported ADRs suspected to be related to medications transmitted through mothers' milk from 1 January 2013 to 1 July 2023. The data were categorized by reporting time, infant age and sex, seriousness and type of ADR, and the medications involved.</p><p><strong>Results: </strong>A total of 922 suspected ADRs were reported in breastfed infants. Serious ADRs accounted for 133 cases (14%), with 15 reported fatalities, primarily associated with methadone (n = 11) and diamorphine (n = 3). COVID-19 vaccines were linked to half of the suspected ADR reports (n = 479, 52%), while serious ADRs were mainly associated with nervous system drugs (n = 73, 43%), particularly anticonvulsants and opioids. Most cases (n = 511, 55%) occurred in infants aged between 1 month and 1 year.</p><p><strong>Conclusions: </strong>The reporting of 922 ADRs in breastfed infants over a decade, compared to the estimated millions of infants exposed to medications via mothers' milk annually in Europe, suggests a very low reporting rate of suspected ADRs. This finding emphasizes the significant challenges in postmarketing surveillance and suggests that underreporting remains a critical concern in pharmacovigilance.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Space travel-associated motion sickness and its treatment.","authors":"Jay C Buckey, Mimi Lan, Lionel D Lewis","doi":"10.1002/bcp.70056","DOIUrl":"https://doi.org/10.1002/bcp.70056","url":null,"abstract":"<p><p>On Earth, motion sickness is often just a nuisance that can spoil a car ride, fishing trip, or visit to an amusement park. In space, however, motion sickness can be hazardous. Vomiting due to motion sickness while in a space suit could lead to aspiration, poor visibility and damage to space suit systems. The effects motion sickness has on alertness and mental performance are undesirable when critical operations are underway. Although motion sickness has been an issue for space travellers since the beginning of human space exploration, the range of medications and routes of administration have not changed appreciably since the early days of spaceflight, which spans more than 40 years. This review presents the main therapeutics available for space-induced motion sickness, the routes of administration available, and the challenges for administering them in space while minimizing major side effects.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evaluation of the acute effects of single-dose TPN171 on semen quality in healthy Chinese male volunteers.","authors":"Yuzhuo Yang, Zhe Zhang, Lei Li, Zhicheng Jiang, Jiaxiang Juan, Huaqing Duan, Zhen Wang, Hui Jiang","doi":"10.1002/bcp.70049","DOIUrl":"https://doi.org/10.1002/bcp.70049","url":null,"abstract":"<p><strong>Aims: </strong>TPN171 is a novel phosphodiesterase type 5 inhibitor for the treatment of erectile dysfunction. This study aimed to assess the immediate impact of a single dose of TPN171 (10 mg) on semen quality in healthy male Chinese volunteers. Additionally, the study investigated the exposure of TPN171 in seminal plasma and observed the safety of TPN171 in the participants.</p><p><strong>Methods: </strong>Eighteen healthy male volunteers were enrolled in this double-blind, randomized, placebo-controlled, 2-period, 2-sequence, crossover study. Semen samples were collected to compare semen parameters between the TPN171 and placebo groups. The concentrations of TPN171 were measured in seminal plasma and blood plasma to calculate the ratio of TPN171 concentration in seminal plasma to that in blood plasma, along with the exposure level and percentage of TPN171 in the seminal plasma.</p><p><strong>Results: </strong>The administration of a single 10-mg dose of TPN171 did not result in statistically significant effects on sperm motility, count, density, morphology, viscosity or volume in healthy male Chinese volunteers. The ratio of TPN171 concentration in seminal plasma to that in blood plasma was 0.72, with the amount of TPN171 in the seminal plasma measured at 78.5 ng. The percentage of exposure to the administered dose (10 mg) was 0.00085%. No adverse events were reported in the TPN171 group.</p><p><strong>Conclusion: </strong>The findings indicate that a single oral dose of 10 mg TPN171 did not induce acute effects on semen quality in healthy male Chinese volunteers. The exposure of seminal plasma to TPN171 was <0.001% of the administered dose.</p><p><strong>Clinical trial registration number: </strong>NCT05585931.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bo-Hao Tang, Shu-Meng Fu, Li-Yuan Tian, Xin-Fang Zhang, Bu-Fan Yao, Wei Zhang, Yue-E Wu, Yue Zhou, Ya-Kun Wang, Guo-Xiang Hao, John van den Anker, Yi Zheng, Wei Zhao
{"title":"Machine learning approach for dosage individualization of azithromycin in children with community-acquired pneumonia.","authors":"Bo-Hao Tang, Shu-Meng Fu, Li-Yuan Tian, Xin-Fang Zhang, Bu-Fan Yao, Wei Zhang, Yue-E Wu, Yue Zhou, Ya-Kun Wang, Guo-Xiang Hao, John van den Anker, Yi Zheng, Wei Zhao","doi":"10.1002/bcp.70050","DOIUrl":"https://doi.org/10.1002/bcp.70050","url":null,"abstract":"<p><strong>Aims: </strong>The uncertainty about the efficacy and safety of currently used azithromycin dosing regimens in children warrants individualized therapy. The area under the plasma concentration-time curve over 24 h (AUC<sub>0-24</sub>) of azithromycin correlates best with its effectiveness. The aim of this study was to evaluate the ability of machine learning (ML) to predict the AUC<sub>0-24</sub> of azithromycin in children with community-acquired pneumonia.</p><p><strong>Methods: </strong>Various ML algorithms were used to build ML models based on simulated pharmacokinetic profiles from a published population pharmacokinetic model. A priori-ML model predicted AUC<sub>0-24</sub> using patients' characteristics and after the trough concentration (C<sub>0</sub>) became available, a posteriori-ML model was built for improved prediction. Statistical methods and pharmacodynamic (PD) evaluation methods were used to evaluate the ML model's predictive accuracy in a real-world study. ML-optimized doses were evaluated by calculating the probability of PD target attainment in virtual trials compared with guideline-recommended doses.</p><p><strong>Results: </strong>The AUC<sub>0-24</sub> can be predicted by priori-ML model using the CatBoost algorithm with dosing regimen and two covariates as predictors (weight, alanine aminotransferase) before initial administration. A posteriori-ML model using CatBoost algorithm was built with adding C<sub>0</sub> as a predictor. In real-world validation, the mean absolute prediction error of the priori-ML and posteriori-ML models was less than 30%. The accuracy (determining whether the PD target is met) of the priori-ML model was 76.3%, whereas that of the posteriori-ML model increased to 90.4%.</p><p><strong>Conclusions: </strong>ML models were established to predict the AUC<sub>0-24</sub> of azithromycin successfully and could be used for individual dose adjustment in children before treatment and after obtaining C<sub>0</sub>.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Soyoung Park, Ah Young Lee, Jonghyun Jeong, Kyu-Nam Heo, Ji Min Han, Young-Mi Ah, Ju-Yeun Lee
{"title":"Incidence and spectrum of typical complications associated with immunosuppressant use in rheumatic disease: A nationwide retrospective study.","authors":"Soyoung Park, Ah Young Lee, Jonghyun Jeong, Kyu-Nam Heo, Ji Min Han, Young-Mi Ah, Ju-Yeun Lee","doi":"10.1002/bcp.70054","DOIUrl":"https://doi.org/10.1002/bcp.70054","url":null,"abstract":"<p><strong>Aim: </strong>To estimate the incidence and characteristics of typical complications associated with immunosuppressant therapy across various types of rheumatic disease (RD).</p><p><strong>Methods: </strong>We conducted a retrospective analysis using Korean claims data, including patients who were first diagnosed with rheumatic disease (rheumatoid arthritis, spondyloarthrosis, lupus erythematosus, vasculitis, sclerosis, Sjögren's syndrome, and polymyalgia rheumatica) and initiated immunosuppressant therapy between 2015 and 2018. We focused on several typical complications, including infections, cancer, cardiovascular complications, bone marrow suppression, gastrointestinal complications, diabetes, interstitial lung disease, demyelinating disease, acute kidney injury, and hepatotoxicity.</p><p><strong>Results: </strong>Among 464 753 patients prescribed immunosuppressants, 59 548 initiated treatment following their RD diagnosis. The most prevalent complications included opportunistic infections (60.6 events per 1000 person-years), serious infections (41.1), hypertension (31.5), diabetes (18.3), and cancer (14.1). Most complications peaked in the first month after treatment initiation. While the risk of serious infections and cancer increased with age, the incidence of opportunistic infections did not significantly vary. Furthermore, risk of serious infection or cancer did not significantly differ among RD types.</p><p><strong>Conclusions: </strong>This investigation elucidated the incidence and spectrum of typical complications associated with immunosuppressants among patients with RD, using a vast real-world dataset to highlight key safety concerns.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Best fit framework synthesis of qualitative studies on factors associated with medication nonadherence in people with type 2 diabetes using the COM-B model.","authors":"Vivien Teo, John Weinman, Kai Zhen Yap","doi":"10.1002/bcp.70059","DOIUrl":"https://doi.org/10.1002/bcp.70059","url":null,"abstract":"<p><p>This review aimed to synthesize factors associated with medication nonadherence among people with type 2 diabetes (PwT2D), using the Capability, Opportunity, Motivation and Behaviour (COM-B) model as the a priori model. Studies published between January 2014 and April 2024 were searched on five databases. Studies were included if they recruited PwT2D aged >18 years, investigated factors associated with adherence to oral and/or nonoral medications for diabetes, used qualitative research methods, were conducted in a community setting, were in English language and had accessible full-text articles. Best fit framework synthesis was undertaken, which led to the development of a hypothesized COM-B variant model specific to medication nonadherence among PwT2D. Study quality was assessed using published criteria to evaluate whether the study was adequately reported. Twenty-two studies were included. Factors were mapped onto the COM-B model: physical capability (e.g., difficulty injecting insulin independently), psychological capability (e.g., understanding about diabetes), physical opportunity (e.g., cost of medication), social opportunity (e.g., quality of communication and relationship with healthcare providers), automatic motivation (e.g., habit formation) and reflective motivation (e.g., perceived necessity and effectiveness of medications). Reflective motivation had the most themes, while physical capability only had one theme. Personality was a theme that could not be mapped onto the model. Interactions between some COM-B components (e.g., capability and motivation) were observed. This theoretically grounded synthesis may facilitate future intervention development by formulating a programme theory and identifying behaviour change techniques to address the identified factors.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuhao Wang, Chao Yu, Mengyue Hu, Lu Wang, Meixia Chen, Hanmo Liu, Nan Wu, Jie Hou
{"title":"Safety, tolerability, pharmacokinetics and pharmacodynamics of HSK31858, a novel oral dipeptidyl peptidase-1 inhibitor, in healthy volunteers: An integrated phase 1, randomized, double-blind, placebo-controlled, single- and multiple-ascending dose study.","authors":"Yuhao Wang, Chao Yu, Mengyue Hu, Lu Wang, Meixia Chen, Hanmo Liu, Nan Wu, Jie Hou","doi":"10.1002/bcp.70027","DOIUrl":"https://doi.org/10.1002/bcp.70027","url":null,"abstract":"<p><strong>Aim: </strong>Dipeptidyl peptidase-1 (DPP-1) inhibitors have been studied for the treatment of neutrophil-mediated inflammatory diseases including bronchiectasis, bronchial asthma and cystic fibrosis. This study evaluated the pharmacokinetics, pharmacodynamics, safety and tolerability of DPP-1 inhibitor HSK31858 in healthy Chinese volunteers.</p><p><strong>Methods: </strong>Volunteers in Part A randomly received single doses of HSK31858 (15, 40, 60 and 80 mg) or placebo in fasted states. The 40-mg cohort also received HSK31858 40 mg or placebo in fed states. In Part B, volunteers randomly received HSK31858 10, 20 and 40 mg or placebo once daily for 28 days in fasted states. The primary endpoints were safety and tolerability of HSK31858.</p><p><strong>Results: </strong>Among 38 volunteers in Part A and 36 in Part B, HSK31858 was well tolerated; no deaths, serious adverse events, or discontinuations due to adverse events occurred. The median T<sub>max</sub> was 0.75 to 1.0 h and the mean terminal t<sub>1/2</sub> was 16.5 to 21.0 h in the fasted state with single doses of HSK31858. Both C<sub>max</sub> and AUC<sub>0-t</sub> exhibited a dose-dependent rise. Food had no effect on AUC. Multiple doses of HSK31858 demonstrated a similar pharmacokinetics profile, with about 2-fold accumulation in AUC. HSK31858 dose-dependently inhibited neutrophil count-normalized neutrophil elastase (NE<sub>norm</sub>) activity. The maximal percentage decrease in NE<sub>norm</sub> activity relative to baseline during 28 days of HSK31858 treatments was 13.6% and 76.4% with HSK31858 10 and 40 mg once-daily, respectively.</p><p><strong>Conclusion: </strong>HSK31858 was safe and well tolerated. The pharmacokinetics and pharmacodynamics profile of HSK31858 supports further clinical development for the treatment of neutrophil-mediated inflammatory diseases.</p><p><strong>Trial registration: </strong>NCT05663593.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to “Incidence and trend of cardiac events among children and young adults exposed to psychopharmacological treatment (2006–2018): A nationwide register-based study”","authors":"","doi":"10.1002/bcp.70058","DOIUrl":"10.1002/bcp.70058","url":null,"abstract":"<p>\u0000 <span>Elmowafi, H</span>, <span>Kindblom, JM</span>, <span>Halldner, L</span>, <span>Gyllenberg, D</span>, <span>Naumburg, E</span>. <span>Incidence and trend of cardiac events among children and young adults exposed to psychopharmacological treatment (2006–2018): A nationwide register-based study</span>. <i>Br J Clin Pharmacol</i>. <span>2025</span>; <span>91</span>(<span>3</span>): <span>817</span>–<span>828</span>. doi:10.1111/bcp.16321</p><p>In Figure 2B, the word male and females <b>are</b> missed in the legend as illustrated below.</p><p>In Figure 2C, the word male and females are missed in the legend the word male and female should be added in the legend as illustrated below.</p><p>In figure 3A, the word male and female should be added in the legend as illustrated below.</p><p>In figure 3B, the word male and female should be added in the legend as illustrated below.</p><p>In figure 3C, the word male and female should be added in the legend as illustrated below.</p><p>We apologize for the errors.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 5","pages":"1520-1523"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bcp.70058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Magnus Andreas Hvistendahl, Mats Bue, Pelle Hanberg, Sara Kousgaard Tøstesen, Sofus Vittrup, Maiken Stilling, Kristian Høy
{"title":"First-time cefuroxime target tissue concentrations in long-lasting spine surgery: Continuous evaluation after repeated weight-dosed administrations.","authors":"Magnus Andreas Hvistendahl, Mats Bue, Pelle Hanberg, Sara Kousgaard Tøstesen, Sofus Vittrup, Maiken Stilling, Kristian Høy","doi":"10.1002/bcp.70052","DOIUrl":"https://doi.org/10.1002/bcp.70052","url":null,"abstract":"<p><strong>Aims: </strong>Antimicrobial prophylaxis is central in preventing postoperative spine infections, yet knowledge on clinical target spine tissue concentrations remain limited. Current dosing regimens often involve fixed doses based on empirical knowledge, surrogate measures, non-clinical evidence and methodology of variying quality. The objective was to continuously evaluate peri- and postoperative cefuroxime target tissue concentrations in long-lasting spine surgery.</p><p><strong>Methods: </strong>Twenty patients scheduled for spine deformity surgery with hypotensive anaesthesia completed the study. Weight-dosed cefuroxime was administered intravenously (20 mg/kg) to all patients preoperativey and after 4 h. Microdialysis probes were placed in vertebral bone (intraoperative sampling), paravertebral muscle, subcutaneous tissue and profoundly/superficially in the wound. Microdialysates and plasma samples were obtained for up to 12 h. The primary endpoint was the time with cefuroxime concentrations above the minimal inhibitory concentration for Staphylococcus aureus of 4 μg/mL as a percentage (%fT>MIC4).</p><p><strong>Results: </strong>The median cefuroxime %fT>MIC4 (range) of patients' individual surgery time was 100% (100-100) in all investigated tissues and plasma. Median cefuroxime %fT>MIC4 (range) in the first dosing interval was 93% (93-93) in vertebral bone, paravertebral muscle and subcutaneous tissue, and 100% (99-100) in plasma. Median cefuroxime %fT>MIC4 (range) in the second dosing interval was 85% (52-100) in paravertebral muscle, 94% (52-100) in subcutaneous tissue, 99% (71-100) in the profound wound, 100% (72-100) in the superficial wound, and 70% (42-100) in plasma.</p><p><strong>Conclusions: </strong>Repeated weight-dosed intravenous cefuroxime administrations (20 mg/kg) provided homogenous and sufficient intraoperative target tissue exposure of cefuroxime (100% fT>MIC4) in long-lasting spine surgery with hypotensive anaesthesia and postoperative exposure (>4 μg/mL) for 5.5-7.5 h.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Romina Lorena de Los Santos-Fernández, Antonio Segovia-Zafra, Guillermo Paz-López, Gonzalo Matilla-Cabello, Hao Niu, Ismael Álvarez-Álvarez, Camilla Stephens, Andrés González-Jiménez, M Isabel Lucena, Raúl J Andrade, Inmaculada Medina-Cáliz
{"title":"Epigenetic modifications in drug-induced liver injury: A systematic review.","authors":"Romina Lorena de Los Santos-Fernández, Antonio Segovia-Zafra, Guillermo Paz-López, Gonzalo Matilla-Cabello, Hao Niu, Ismael Álvarez-Álvarez, Camilla Stephens, Andrés González-Jiménez, M Isabel Lucena, Raúl J Andrade, Inmaculada Medina-Cáliz","doi":"10.1002/bcp.70053","DOIUrl":"https://doi.org/10.1002/bcp.70053","url":null,"abstract":"<p><p>Genetic susceptibility has been identified in idiosyncratic drug-induced liver injury, a potentially severe adverse reaction towards drugs, herbal products and dietary supplements. However, its occurrence cannot be fully explained by the presence of genetic variants in specific genes, suggesting that other factors are involved. Drug-induced liver injury epigenetic signatures could help explain genetic regulatory mechanisms behind this disease and might provide disease biomarkers. This systematic review aims to analyse all available information on epigenetic risk association studies in drug-induced liver injury. The main inclusion criterion was population studies on idiosyncratic drug-induced liver injury with significant risk association analysis between drug-induced liver injury and an epigenetic regulation mechanism. Out of the 7 included articles, 6 focused on DNA methylation and 1 on long noncoding RNA. All of the studies were on antituberculosis drug-induced liver injury and came from Asia. CpG site methylation in the CYP2D6 (odds ratio: 9.19, 95% confidence interval: 3.26-25.89, P < .001) and NAT2 (odds ratio: 8.37, 95% confidence interval: 2.39-29.32, P = .001) promoters conferred the highest risk. Hypomethylation of LINE-1 and Alu transposable elements has potential as antituberculosis drug-induced liver injury biomarkers, showing an area under the curve value of 0.94. To conclude, the studies mainly focused on DNA methylation modifications associated with antituberculosis drug-induced liver injury, with all of them coming from Asia, where tuberculosis is a public health burden. Despite the lack of knowledge in this area, the evidence has shown that DNA methylation alterations in antituberculosis drug-induced liver injury could have potential as a new diagnostic and therapeutic target.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}