BMC Pharmacology & Toxicology最新文献

{"title":"Trends in drug-drug interactions for new drug clinical trials in China over the past 10 years (2013-2022).","authors":"Jianxiong Zhang, Jingxuan Wu, Jiangshuo Li, Meixia Liu, Shaodan Liu, Ruirui He, Ruihua Dong","doi":"10.1186/s40360-025-00905-3","DOIUrl":"10.1186/s40360-025-00905-3","url":null,"abstract":"<p><p>The number of drug-drug interaction (DDI) clinical trials in China has increased rapidly in recent years. The aim of this study was to summarize and analyze DDI clinical trials in China over the past 10 years. We conducted a cross-sectional study of DDI clinical trials registered in the Chinese Center for Drug Evaluation (CDE) from September 6, 2013 to December 31, 2022. All related registration information disclosed on the CDE website were summarized and analyzed. Although the number of DDI clinical trials conducted before 2017 was relatively low, it increased markedly after 2017. The average duration of DDI clinical trials was 85.83 ± 100.99 days from 2013 to 2019 and 107.16 ± 98.57 days from 2020 to 2022. The duration of rifampicin use was 5-19 days, and the investigational drug was administered after 5-14 days of rifampicin use. Itraconazole was administered for 4-17 days, and the investigational drug was administered after 3-10 days of itraconazole use. Clinical trials of drug-drug interactions have recently increased due to the development of new drugs and the updated policies regulating drug registration and marketing. Although the designs of clinical trials comply with the new guidelines, the duration of the administration of interacting drugs still varies widely. Optimizing protocol designs can shorten the implementation period of clinical trials and reduce the costs of drug marketing.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"66"},"PeriodicalIF":2.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676574","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}

{"title":"Risk comparison of adverse reactions between gemcitabine monotherapy and gemcitabine combined with albumin-bound paclitaxel in pancreatic cancer: insights from the FDA Adverse Event Reporting System (FAERS) database.","authors":"Puen Jiang, Kezhen Zong, Dadi Peng, Baoyong Zhou, Zhongjun Wu","doi":"10.1186/s40360-025-00884-5","DOIUrl":"10.1186/s40360-025-00884-5","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic cancer (PC) is a highly aggressive malignancy with limited treatment options. Although gemcitabine monotherapy (G treatment) has long been a standard treatment, combination therapies, such as gemcitabine with albumin-bound paclitaxel (AG treatment), have shown improved outcomes and were approved by the FDA for the PC. However, the AG treatment is also associated with increased adverse events (AEs), which remain inadequately evaluated in real-world settings.</p><p><strong>Methods: </strong>We utilized the FDA Adverse Event Reporting System (FAERS) to conduct a large-scale pharmacovigilance analysis comparing the safety profiles of G and AG treatments for PC. By analyzing adverse event data from the third quarter of 2013 to the second quarter of 2024 and quantifying AE signals with reporting odds ratio (ROR) and proportional reporting ratio (PRR) methods, we compared the risk of AEs between the groups. Time to onset (TTO), subgroup and logistic regression analyses were also performed.</p><p><strong>Results: </strong>The study revealed a higher proportion of male (n = 2307, 54.1%) and elderly patients (age ≥ 65years, n = 2172, 50.9%) in the AG treatment group compared to the G treatment group. We found 17 preferred terms with positive signals at the top 50 common AEs, especially in gastrointestinal and blood systems. Cardiac and neurological AEs also needed to be vigilant. Biliary sepsis and infectious enterocolitis were newly identified AEs and deserve attention. Median TTO was 34 (IQR: 8-103) days (G) and 41 (IQR: 10-104) days (AG), with most AEs occurring within the first month (48.3% and 44%). Subgroup analysis revealed that male patients using the AG treatment had the highest risk of immune-mediated hepatitis (ROR = 23.51, 95% CI = 3.21-172.1), while elderly patients had elevated risks for presyncope (ROR = 24.84, 95% CI = 3.40-181.28) and falls (ROR = 18.60, 95% CI = 2.53-136.97). Logistic regression showed higher-risk fatal outcomes in males (adjusted OR = 1.42, 95% CI = 1.15-1.76, P < 0.01) and elderly patients (adjusted OR = 1.36, 95% CI = 1.10-1.69, P < 0.01).</p><p><strong>Conclusion: </strong>This research offers critical safety insights in real-world settings, emphasizing patients at heightened AEs risk and informing clinical decision-making in PC treatment.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"65"},"PeriodicalIF":2.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662028","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}

{"title":"Oxidative stress and anti-oxidant status in children with sepsis.","authors":"Hatice Feray Arı, Murat Arı, Serdal Ogut","doi":"10.1186/s40360-025-00895-2","DOIUrl":"10.1186/s40360-025-00895-2","url":null,"abstract":"<p><strong>Background: </strong>Sepsis is a life-threating cause in childhood ages. The recognition and treatment early are significant for decreasing mortality. Sepsis has many factors and various biomarkers function in the pathogenesis, the stress indicators oxidants increased and antioxidants decreased. The objective of our study was to investigate the levels of thiol disulfides with and without sepsis in a pediatric intensive care unit (PICU).</p><p><strong>Materials and methods: </strong>A cohort study was conducted between October 2022 and March 2023 at the PICU, comprising 64 with sepsis and 62 children without sepsis. Blood samples from sepsis and the control group were collected and centrifuged. Subsequently, the samples were stored at -80 °C until the day of the experiment. Once the requisite number of patients had been enrolled, the thiol-disulfide values in the collected samples were analysed in accordance with the ELISA kit method.</p><p><strong>Results: </strong>The research parameters investigated, namely total oxidant status, plasma 8-OHdG, total-native thiol and native/total thiol percent ratio, were found to be considerably elevated in the sepsis group in comparison to the control (p < 0.05). Furthermore, the oxidative stress parameters investigated (total antioxidant status, paraoxonase 1 activity, disulfide, disulfide/native thiol percent ratio, disulfide/total thiol percent ratio) were found to be significantly lower in the sepsis group than in control (p < 0.05).</p><p><strong>Conclusions: </strong>In our study as well, we detected all antioxidant parameters are low and oxidant parameters are statistically significantly higher in sepsis. Our study posits that thiol-disulfide levels have the potential to serve as a diagnostic tool in conjunction with traditional established biomarkers of inflammation in critically ill children in the PICU who are being treated for sepsis.</p><p><strong>Clinical trial registration: </strong>Not applicable.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"64"},"PeriodicalIF":2.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662027","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}

{"title":"A disproportionality analysis of adverse events associated with loop diuretics in the FDA Adverse Event Reporting System (FAERS).","authors":"ZeHu Xue, Xi Liu, QiFeng Liu, XiuMing Yang, LiXia Yu","doi":"10.1186/s40360-025-00890-7","DOIUrl":"10.1186/s40360-025-00890-7","url":null,"abstract":"<p><strong>Background: </strong>Loop diuretics, including furosemide, torsemide, and bumetanide, are widely utilized in the management of volume overload-related conditions. Although previous studies have extensively documented risks such as electrolyte imbalances, ototoxicity, and nephrotoxicity, real-world evidence regarding novel or underrecognized adverse event (AE) signals remains limited and underexplored.</p><p><strong>Methods: </strong>Using data from the Food and Drug Administration Adverse Event Reporting System (FAERS) from the first quarter of 2004 to the third quarter of 2024, we conducted a disproportionality analysis integrating Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM), combined with multivariate logistic regression. It is considered a significant signal when one of the four indicators meets the criteria. The temporal characteristics were elucidated via time-to-onset (TTO) analysis.</p><p><strong>Results: </strong>A total of 24,875 AE reports were analyzed, with furosemide accounting for 89.18%, torsemide for 8.33%, and bumetanide for 2.47%. Commonly reported risks included electrolyte imbalances, fluid balance disorders, and nephrotoxicity. Several novel safety signals were identified: furosemide was significantly associated with vitamin B1 deficiency (TTO = 71 days), Wernicke's encephalopathy (TTO = 2167 days), and gastrointestinal mucosal pigmentation (TTO = 549.1 days). Torsemide was associated with palisaded neutrophilic granulomatous dermatitis (TTO = 62.8 days), systemic infection (TTO = 548.3 days), pemphigoid (TTO = 470.6 days), bleeding events (involving the respiratory, gastrointestinal, and urinary tracts), and prolonged prothrombin time (TTO = 159.4 days). Bumetanide was linked to blood ketone body increased (TTO = 9.0 days), metabolic encephalopathy (TTO = 1786.0 days), and immune hypersensitivity reactions (Stevens-Johnson syndrome, pemphigoid, and lip swelling).</p><p><strong>Conclusion: </strong>This study identified both common and drug-specific AEs associated with loop diuretics, particularly focusing on the metabolic and immune risks of long-term use. To enhance patient safety, clinicians are advised to develop personalized monitoring strategies based on individual patient characteristics. For furosemide, monitoring and supplementation of vitamin B1 and magnesium are recommended. For torsemide, attention should be given to coagulation function and delayed hypersensitivity reactions. For bumetanide, close monitoring of metabolic disorders and immune-related skin lesions is essential. These findings support individualized therapy and precise pharmacovigilance, ensuring safer and more effective use of loop diuretics.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"63"},"PeriodicalIF":2.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647064","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}

{"title":"A new RP-HPLC approach for estimation of potential impurities of Fosamprenavir - method development and validation.","authors":"Ramreddy Godela, Vinod Kumar Nelson, Mohana Vamsi Nuli, Pavan Kumar Jaini, Shilpi Pathak, Krishnaphanisri Ponnekanti, Punna Rao Suryadevara, Gowri Sankararao Burle, Vinyas Mayasa, Kavindra Kumar Kesari","doi":"10.1186/s40360-025-00892-5","DOIUrl":"10.1186/s40360-025-00892-5","url":null,"abstract":"<p><p>The current work aims to develop a reliable and robust RP-HPLC method for analyzing Fosamprenavir and its potential impurities, including isomer, amino, propyl, nitro, and Amprenavir. The method used a Zobrax C18 column with a mobile phase of 0.1% V/V orthophosphoric acid in water and acetonitrile in gradient elution at a flow rate of 1 mL/min to accomplish efficient separation with detection at 264 nm and column temperature of 30 ± 2⁰C. A diluent with a 1:1 water-to-acetonitrile ratio was used to prepare standard and sample solutions. The developed approach was validated as per ICH Q2(R1) guidelines. Fosamprenavir, Amino, Propyl, Isomer, Nitro impurities, and Amprenavir impurities were eluted at retention time (RT) of 5.3 min, 2.3 min, 4.3 min, 4.7 min, 8.1 min and 8.6 min correspondingly with good resolution within a 10-minute run time. Method validation confirmed system suitability, linearity (R² = 0.999), good sensitivity (LOD/LOQ), specificity, precision (% RSD: 0.5-1.7), accuracy (% recovery: 90.9-104.3%), and robustness. The optimized approach excelled existing methods in lower retention time, run time, sensitivity, and linearity for all potential impurities, making it a novel and trustworthy method for monitoring Fosamprenavir drug quality and assessing stated impurities. The established method allows precise measurement of Fosamprenavir and related substances, supporting drug safety and regulatory compliance.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"60"},"PeriodicalIF":2.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633324","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}

{"title":"A single-dose, four-cycle, fully repetitive crossover bioequivalence of dabigatran etexilate in Chinese.","authors":"Zhuan Yang, Qin Li, Danfeng Yu, Xiaojuan Zhang, Ying Wang, Shijing Liu, Lu Chen, Yan Zhou, Chen Zeng, Yan Zeng, Chen Cai, Yun Xiong, Qian Zhang, Na Li, Peng Du, Lin Liu, Jiyu Chen, Yan He","doi":"10.1186/s40360-025-00896-1","DOIUrl":"10.1186/s40360-025-00896-1","url":null,"abstract":"<p><strong>Purpose: </strong>Among healthy Chinese subjects, two capsules of dabigatran etexilate were tested for bioequivalence.</p><p><strong>Method: </strong>Fifty healthy subjects were recruited for each of the fasting and postprandial trials in a randomized, two-sequence, open-label, four-cycle, fully replicated trial design of a single 150 mg dose of either the test or the reference formulation of dabigatran etexilate capsules in the fasting and postprandial states. The blood concentration of dabigatran at different time points after administration was determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The bioequivalence of the two formulations was evaluated by means of the main pharmacokinetic parameters and relative bioavailability.</p><p><strong>Results: </strong>There were 39 males and 11 females in both fasting and postprandial groups. The age, height, weight and BMI of subjects in the fasting group were 19.0-41.0 years old, 148.5-182.0 cm, 46.1-81.0 kg and 19.2-25.7 kg/m², respectively, and those in the postprandial group were 18.0-43.0 years old, 145.5-182.5 cm, 45.2-82.0 kg and 19.2-25.9 kg/m², respectively. The 90% confidence intervals (CIs) for the geometric mean ratios of C_max, AUC_0-t and AUC_0-∞ for the total dabigatran in fasting test and reference formulations were 92.41-104.30%, 92.59-104.27% and 93.10-104.27%, respectively. The 90% CIs for the geometric mean ratios of three important parameters C_max, AUC_0-t, and AUC_0-∞ pertaining to the total dabigatran in the postprandial test and reference formulations were 97.29-107.77%, 100.43-107.96%, and 100.19-107.40%, respectively. The 90% CIs for the geometric mean ratios of the main pharmacokinetic parameters of the test and reference formulations were in the ranged from 80. 00-125. 00%, and the upper limits of the 90% CIs for the intraindividual variability ratios were ≤2.5. No serious adverse events (SAEs) occurred in the fasting and postprandial groups.</p><p><strong>Conclusion: </strong>The 2 dabigatran etexilate capsules were bioequivalent in both fasting and postprandial states and had favorable safety profile.</p><p><strong>Trial registration: </strong>The enrollment process in this study was finalized on the \"Chemical Drug Bioequivalence Trial Record Information Platform.\" ( http://www.chinadrugtrials.org.cn , 04/07/2023, CTR20231968).</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"62"},"PeriodicalIF":2.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633335","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}

{"title":"Adverse event profile of crizotinib in real-world from the FAERS database: a 12-year pharmacovigilance study.","authors":"Huan Zhang, Yunrui Song, Fantong Xia, Yunchang Liu, Lu Zhang, Jieying Yang, Honglei Tu, Bin Long, Jiangdong Sui, Ying Wang","doi":"10.1186/s40360-025-00859-6","DOIUrl":"10.1186/s40360-025-00859-6","url":null,"abstract":"<p><strong>Aim: </strong>Crizotinib, an anaplastic lymphoma kinase tyrosine kinase inhibitor (ALK-TKI). It gained approval from the U.S. Food and Drug Administration (FDA) specifically for treating ALK-positive non-small cell lung cancer (NSCLC). The objective of the present investigation was to evaluate adverse events (AEs) associated with crizotinib in real-world by employing data mining on the U.S. FDA Adverse Event Reporting System (FAERS).</p><p><strong>Methods: </strong>Data encompassing AEs linked to crizotinib from 2011 to 2023 were gathered. Disproportionality analyses, which involved the utilization of reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS), were employed for analytical purposes.</p><p><strong>Results: </strong>A total of 10,226 reports documenting crizotinib-associated AEs were extracted from the FAERS database. Out of these, 147 preferred terms (PTs) displaying significant disproportionality were identified concurrently across all four algorithms. The most frequently observed AEs included increased transaminases, bradycardia, prolonged QT, nausea, vomiting, diarrhea, constipation, visual impairment, and interstitial lung disease, which were consistent with previous reports from clinical trials. Additionally, unexpected significant AEs such as deep vein thrombosis, pneumocystis jirovecii pneumonia, gastrointestinal amyloidosis, and hepatic coma were also observed.</p><p><strong>Conclusion: </strong>Crizotinib offers therapeutic benefits but is also accompanied by various risks in the form of AEs. Our study findings align with previous clinical observations, and furthermore, we have identified unforeseen serious AEs. This discovery serves as a novel basis for the monitoring of dosages and the identification of risks associated with crizotinib.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"61"},"PeriodicalIF":2.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633368","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}

{"title":"Dapagliflozin attenuates metabolic dysfunction-associated steatotic liver disease by inhibiting lipid accumulation, inflammation and liver fibrosis.","authors":"Xingyu Fan, Yueyue Wang, Yue Wang, Hao Duan, Yijun Du, Tianrong Pan, Xing Zhong","doi":"10.1186/s40360-025-00898-z","DOIUrl":"10.1186/s40360-025-00898-z","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a globally prevalent liver disease, closely linked to the rising incidence of obesity, diabetes, and metabolic syndrome. Dapagliflozin (DaPa), a sodium-glucose cotransporter-2 inhibitor, is primarily prescribed for diabetes management. It has shown potential efficacy in managing MASLD in clinical settings. However, the molecular mechanisms underlying the effects of DaPa on MASLD remain poorly understood. Hence, we aimed to investigate the role of and mechanisms underlying DaPa in MASLD.</p><p><strong>Methods: </strong>Male diet-induced obese (DIO) C57BL/6J mice were injected with streptozotocin (STZ), followed by a high-fat diet regimen to stimulate metabolic dysfunction. Subsequently, they received DaPa via gavage for 5 weeks. Hepatic lipid accumulation, pathological alterations, inflammatory markers, and liver fibrosis were assessed.</p><p><strong>Results: </strong>DaPa administration reduced liver fat accumulation in DIO mice. Additionally, it decreased oxidative stress and lipid peroxide levels, which was attributed to the upregulation of glutathione and the downregulation of malondialdehyde and reactive oxygen species levels. Notably, DaPa downregulated the inflammatory response and reduced liver fibrosis.</p><p><strong>Conclusions: </strong>DaPa protects against MASLD by inhibiting lipid accumulation, inflammation, oxidative stress, and liver fibrosis.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"59"},"PeriodicalIF":2.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613054","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}

{"title":"AMD1, a cardiotoxicity target for Maduramicin.","authors":"Zi-Feng Xie, Han-Meng Liu, Jia-Fan Zhao, Yuan Gao, Yuan-Long Zhao, Jia-Yue Zheng, Xiao-Wei Pei, Ning Zhang, Ge Tian","doi":"10.1186/s40360-025-00897-0","DOIUrl":"10.1186/s40360-025-00897-0","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study was to investigate AMD1 cardiotoxicity function for Maduramicin (Mad).</p><p><strong>Methods: </strong>SD rats were divided into control (Control) group and Mad treatment (3.5 mg/kg) group (Mad). After treatment with Mad for seven days, the levels of LDH and CK-MB in serum were detected, H&E staining and TUNEL staining were performed. In vitro, 1.0 μm Mad was used for the subsequently experiment, observing cell apoptosis from Flow cytometry. Caspase-3 and AMD1 were detected in Western blotting. Flow cytometry and Western blotting were also performed after use of siRNA-AMD1-1. Then, analysis AMD1 potential function in cardiotoxicity from bioinformatics techniques including GO, KEGG, PPI, immune infiltration and molecular docking.</p><p><strong>Result: </strong>Maduramicin has myocardial toxic effects in vivo and vitro, which with AMD1 raised. When AMD1 was knocked down, toxic effects of Mad were alleviated. Apoptosis, proliferation and inflammation were the major pathophysiological changes in myocardial apoptosis process with AMD1-knockdown. This process involved in IL1A, IL1B, PTGS2, VEGFA, VEGFC and HBEFG, as hub genes related AMD1 cardiotoxicity function for Maduramicin. AMD1 was knocked down, their microenvironment changes: Effector memory CD4 T cell and Natural killer cell were more infiltrated, and Mast cell were less infiltrated.</p><p><strong>Conclusion: </strong>Mad exerted cardiotoxic effects by upregulating the AMD1 gene, which may be associated with cell apoptosis, proliferation and inflammatory response. AMD1 also had cardiotoxicity function, by the impact of both myocardial cells and the microenvironment they live.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"55"},"PeriodicalIF":2.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603656","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}

{"title":"Post-market safety profile of cefiderocol: a real-world pharmacovigilance exploratory analysis based on U.S. FDA adverse event reporting system (FAERS).","authors":"Hao Lin, Chen Zhu, Shuang Liu, Yingmin Bi, Jindong Hu, Mohan Ju","doi":"10.1186/s40360-025-00894-3","DOIUrl":"10.1186/s40360-025-00894-3","url":null,"abstract":"<p><strong>Background: </strong>Cefiderocol is a new drug class, which is approved to treat Gram-negative bacteria infection. Its approval for marketing has provided clinicians with additional options for treating antimicrobial resistant gram-negative infections. The aim of our study was to assess the safety profiles of cefiderocol in real-world through data mining of the United States Food and Drug Administration Adverse Event Reporting System (FAERS).</p><p><strong>Methods: </strong>We included adverse event (AE) reports regarding cefiderocol submitted to the FAERS from 2019 quarter 4 (2019Q4) to 2024 quarter 3 (2024Q3). Disproportionality analyses, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN) and Multi-item Gamma Poisson Shrinker (MGPS) techniques were performed to identify the signals of disproportionate reporting of AEs in patients receiving cefiderocol. A signal of disproportionate reporting was detected if the lower limit of the 95% confidence interval (CI) of ROR > 1, the PRR was ≥ 2(while the Chi-Square of PRR was ≥ 4), the lower limit of 95% CI of the information component (IC025) was > 0, the lower limit of 95% CI of the Empirical Bayes Geometric Mean (EBGM05) was > 2 and at least 3 AEs were reported.</p><p><strong>Results: </strong>A total of 29 significant preferred terms (PTs) were identified among the 592 cefiderocol-associated adverse events (AEs) reports collected from the FAERS database. Cefiderocol-induced adverse events involved 24 System Organ Class (SOC). 29 positive signals of disproportionate reporting are also presented, such as Pathogen resistance (n = 16, ROR 189.35, PRR 184.26, IC 7.52, EBGM 183.89), Systemic candida (n = 3, ROR 138.79, PRR 138.19, IC7.11, EBGM 137.88), Drug resistance (n = 30, ROR 131.96, PRR 125.33, IC6.97, EBGM 125.16), and Drug effect less than expected (n = 6, ROR 68.42, PRR 67.74, IC6.08, EBGM 67.69). The most frequently observed were Death, Drug resistance and Treatment failure.</p><p><strong>Conclusions: </strong>Our findings offer significant evidence regarding the safety profile of cefiderocol in real-world settings. This information may assist clinicians and pharmacists in enhancing their vigilance and improving the overall safety of cefiderocol in clinical practice.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"58"},"PeriodicalIF":2.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11899456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603672","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}