BMC Pharmacology & Toxicology最新文献

{"title":"A disproportionality analysis of real-world events from the FDA Adverse Event Reporting System (FAERS) for Atezolizumab.","authors":"Zhuoyang Li, Ning Zhu, Yuwei Liu, Yan Yu, Tianhong Wang, Congcong Zou, Siman Wang, Xiaofeng Ou","doi":"10.1186/s40360-025-00879-2","DOIUrl":"https://doi.org/10.1186/s40360-025-00879-2","url":null,"abstract":"<p><strong>Background: </strong>An increasing number of clinical studies have highlighted the use of atezolizumab in tumor immunotherapy. However, There is still a lack of comprehensive research on its associated adverse events (AEs). To improve our understanding of its toxicological profile and to provide valuable clinical insights regarding into the effectiveness of immunotherapy, this study utilized data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) to conduct a retrospective analysis of AEs linked to atezolizumab.</p><p><strong>Methods: </strong>We extracted the reports of AEs related to atezolizumab from the FAERS database from the first quarter of 2004 to the first quarter of 2024. We quantified them using the reporting odds ratio (ROR) and proportional reporting ratio (PRR), along with chi-square value (χ²), and conducted systematic classification of the AE signal mining results through SAS 9.4 software.</p><p><strong>Results: </strong>A total of 19,563 valid reports were incorporated, involving 20 distinct system organ class categories. The AEs related to atezolizumab, reported at the preferred term level, mainly encompassed anemia [ROR 2.33, 95% confidence interval (CI) lower limit 2.09, PRR 2.31, χ² 255.977], febrile neutropenia (ROR 2.81, 95% CI lower limit 2.50, PRR 2.79, χ² 333.586), neutrophil count decreased (ROR 2.14, 95% CI lower limit 1.89, PRR 2.13, χ² 150.688), white blood cell count decreased (ROR 2.35, 95% CI lower limit 2.03, PRR 2.34, χ² 136.673), sepsis (ROR 2.21, 95% CI lower limit 1.91, PRR 2.20, χ² 117.741), alanine aminotransferase increased (ALT) (ROR 2.86, 95% CI lower limit 2.44, PRR 2.85, χ² 180.031), and aspartate aminotransferase increased (AST) (ROR 2.79, 95% CI lower limit 2.38, PRR 2.78, χ² 170.955).</p><p><strong>Conclusions: </strong>Apart from various degrees of hepatotoxicity, such as increased ALT and AST, the immune-related hematological toxicity of atezolizumab should also be noted. In clinical practice, healthcare providers should always be vigilant for the occurrence of such medication-related AEs and take measures to enhance the safety of clinical medication use.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"51"},"PeriodicalIF":2.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555741","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":"Computational study on the mechanism of small molecules inhibiting NLRP3 with ensemble docking and molecular dynamic simulations.","authors":"Pingyang Qin, Yuzhen Niu, Jizheng Duan, Ping Lin","doi":"10.1186/s40360-025-00851-0","DOIUrl":"https://doi.org/10.1186/s40360-025-00851-0","url":null,"abstract":"<p><p>NLRP3 (Nucleotide-binding oligomerization domain, LRR and pyrin domain-containing protein 3) is a pivotal regulator of inflammation, with strong implications in gout, neurodegenerative diseases, and various inflammatory conditions. Consequently, the exploration of NLRP3 inhibitors is of great significance for the treatment of diseases. MCC950, NP3-146, compound (3), and YQ128 are four highly bioactive NLRP3 inhibitors that show great potential; however, their mechanism of action is currently limited to targeting the ATP binding region (NACHT site) of the NLRP3 protein. To gain deeper insights into the defining features of NLRP3 inhibitors and to develop more potent inhibitors, it is imperative to elucidate the interaction mechanism between NLRP3 and these inhibitors. In this study, we employ a comprehensive computational approach to investigate the binding mechanism between NLRP3 and representative inhibitors. Utilizing the molecular mechanics/generalized Born surface area (MM/GBSA) method, we calculate the binding free energy and pinpoint the key residues involved in the binding of the four inhibitors to NLRP3. The decomposition of binding free energy by the MM/GBSA method reveals that the residues Val71, Arg195, Ile255, Phe419, Arg422, and Met505, situated around the binding pocket, play a crucial role in conferring the high bioactivity of NLRP3 inhibitors. Furthermore, pharmacophore analysis of the four NLRP3 complexes indicates that the primary interaction between the inhibitors and NLRP3 was mainly hydrophobic interaction. Our study provides a profound understanding of the interaction mechanism between NLRP3 and its inhibitors, identifies the key residues involved, and provides theoretical guidance for the design of more efficient NLRP3 inhibitors.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"49"},"PeriodicalIF":2.8,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539821","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":"Gastrointestinal toxicity of antibody-drug conjugates: a pharmacovigilance study using the FAERS database.","authors":"Yanshuo Shi, Kaiqing Yao, Jianqun Zhao, Yuanyuan Yue, Huizhen Wu","doi":"10.1186/s40360-025-00877-4","DOIUrl":"https://doi.org/10.1186/s40360-025-00877-4","url":null,"abstract":"<p><strong>Background: </strong>Antibody-drug conjugate (ADC) product specifications identify gastrointestinal adverse reactions. Nevertheless, there is a scarcity of comparative studies pertaining to these side effects of similar medications. Special attention is warranted for adverse drug reactions (ADRs) affecting the gastrointestinal system that are inadequately documented in the drug literature.</p><p><strong>Aims: </strong>Utilizing the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), data mining was conducted to analyze gastrointestinal adverse reactions associated with ADCs. This analysis aimed to provide evidence supporting the safe use of ADCs in medical institutions.</p><p><strong>Methods: </strong>We utilized the Openvigil 2.1 platform to extract adverse event data reported for each ADC from the FAERS database, covering the period from the drug's launch until the second quarter of 2024. For data analysis, we employed the reporting odds ratio (ROR) and proportional reporting ratio (PRR) methods.</p><p><strong>Results: </strong>A total of 23,886 adverse event reports were retrieved, with nine ADCs identified as the primary suspected drugs, including 1,517 reports of gastrointestinal adverse events linked to ADCs. The average patient age was 59.69 years, with a higher prevalence of female patients (919 patients, 60.58%) than male patients (319 patients, 24.32%). The gastrointestinal toxicity intensity, ranked from highest to lowest, was as follows: inotuzumab ozogamicin (IO) with ROR = 11.12 and PRR = 10.68, gemtuzumab ozogamicin (GO) with ROR = 7.87 and PRR = 7.54, polatuzumab vedotin (PV) with ROR = 6.47 and PRR = 6.20, brentuximab vedotin (BV) with ROR = 5.79 and PRR = 5.61, sacituzumab govitecan (SG) with ROR = 5.19 and PRR = 4.61, mirvetuximab soravtansine (MS) with ROR = 4.37 and PRR = 3.80, trastuzumab deruxtecan (TD) with ROR = 4.22 and PRR = 3.63, trastuzumab emtansine (TE) with ROR = 3.93 and PRR = 3.85, and enfortumab vedotin (EV) with ROR = 3.26 and PRR = 3.02. Adverse events resulted in 237 deaths, 43 life-threatening cases, and 439 initial or prolonged hospitalizations, with TD being the top ranking for deaths and hospitalizations, followed by TE, which presented the highest mortality rate due to adverse events. The most frequent adverse events were nausea (506 cases), diarrhea (262 cases), vomiting (216 cases), ascites (112 cases), colitis (90 cases), pancreatitis (52 cases), and intestinal obstruction (37 cases).</p><p><strong>Conclusions: </strong>ADCs may increase the risk of gastrointestinal adverse events and thus require vigilant monitoring in clinical practice.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"50"},"PeriodicalIF":2.8,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539826","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":"Prodelphinidin B-2,3,3\"-O-gallate via chemical oxidation of epigallocatechin-3-gallate shows high efficacy inhibiting triple-negative breast cancer cells.","authors":"Jing Wang, Yuna Wang, Shuanggou Zhang, Hongtao Hu, Ruohan Zhang, Chengting Zi, Jun Sheng, Peiyuan Sun","doi":"10.1186/s40360-025-00883-6","DOIUrl":"10.1186/s40360-025-00883-6","url":null,"abstract":"<p><strong>Background: </strong>Triple-negative breast cancer is a clinically aggressive malignancy with poorer outcomes versus other subtypes of breast cancer. Numerous reports have discussed the use of epigallocatechin-3-gallate (EGCG) against various types of cancer. However, the effectiveness of EGCG is limited by its high oxidation and instability. The Notch pathway is critical in breast cancer development and prognosis, and its inhibition is a potential treatment strategy.</p><p><strong>Results: </strong>In this study, we investigated the effects of prodelphinidin B-2,3,3''-O-gallate (named PB2,3,3''/OG or compound 2) via chemical oxidation of EGCG on cell viability and the Notch1 signaling pathway in breast cancer cells. We found that compound 2 showed significant cytotoxicity against triple-negative breast cancer cells, with the half maximal inhibitory concentration (IC₅₀) values ranging 20-50 µM. In MDA-MB453 cells, compound 2 inhibited proliferation, clone formation, and the expression of proteins involved in the Notch1 signaling pathway. Furthermore, compound 2 induced cell cycle arrest and apoptosis. Consistent with the results of in-vitro experiments, treatment with compound 2 significantly reduced tumor growth. Mechanistically, compound 2 directly bound to Notch1 with high binding affinity (dissociation constant: K_D=4.616 × 10^- 6 M).</p><p><strong>Conclusion: </strong>Our finding suggested that compound 2 may be a promising agent for the development of novel anti-cancer therapy options.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"48"},"PeriodicalIF":2.8,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531094","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":"Safety analysis of romiplostim, eltrombopag, and avatrombopag post-market approval: a pharmacovigilance study based on the FDA Adverse Event Reporting System.","authors":"Xiaoling Wang, Yunsong Li, Wei Zhuang","doi":"10.1186/s40360-025-00873-8","DOIUrl":"10.1186/s40360-025-00873-8","url":null,"abstract":"<p><strong>Background: </strong>Romiplostim, eltrombopag, and avatrombopag, as new-generation thrombopoietin receptor agonists (TPO-RAs), have been widely used in the treatment of immune thrombocytopenia (ITP). Given their similar efficacy, a comprehensive evaluation of their safety is crucial for optimizing treatment choices. This study aims to explore the potential safety issues of three major drugs for treating ITP: romiplostim, eltrombopag, and avatrombopag, thereby providing references and research directions for subsequent high-quality clinical studies.</p><p><strong>Methods: </strong>We retrieved data from the FDA Adverse Event Reporting System (FAERS) database from the first quarter of 2018 to the second quarter of 2023. Using reporting odds ratio (ROR), proportional reporting ratio (PRR), bayesian confidence propagation neural network (BCPNN), and multiple gamma poisson shrinkage (MGPS), we mined and analyzed adverse events (AEs) associated with romiplostim, eltrombopag, and avatrombopag. The Designated Medical Event (DME) list from the European Medicines Agency (EMA) was used to screen out the DME of three drugs. Venn analysis was used to screen the specific AEs of each drug.</p><p><strong>Results: </strong>The study included 2,851 cases of romiplostim, 10,297 cases of eltrombopag, and 973 cases of avatrombopag. Venn analysis revealed nine common AEs across the three drugs. The number of significant specific AEs associated with romiplostim, eltrombopag, and avatrombopag were 58, 98, and 15 respectively. DMEs for romiplostim included autoimmune haemolytic anaemia (ROR = 6.1, n = 3), haemolytic anaemia (ROR = 8.13, n = 7), sudden hearing loss (ROR = 5.24, n = 3), haemolysis (ROR = 3.89, n = 3). DMEs for eltrombopag included hepatic infection (ROR = 9.56, n = 6), granulocytopenia (ROR = 2.91, n = 4), autoimmune haemolytic anaemia (ROR = 3.03, n = 5), haemolytic anaemia (ROR = 3.46, n = 10), haemolysis (ROR = 4.65, n = 12), hepatic failure (ROR = 2.51, n = 23). Not a single DME was found for avatrombopag.</p><p><strong>Conclusion: </strong>This study indicates that eltrombopag manifests significant safety signals within the hepatic system. This implies that monitoring liver function during treatment is advisable. Avatrombopag shows relatively lower hepatotoxicity signals; however, further large-scale studies are needed to validate these observations. Moreover, both romiplostim and eltrombopag therapies may be linked to a risk of sudden hearing loss or deafness, which merits clinical attention. These findings offer crucial safety references for clinical drug use. Nevertheless, the causal relationship between the drugs and AEs necessitates further in-depth investigation.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"46"},"PeriodicalIF":2.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522685","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":"Development and validation of a nomogram to predict linezolid-induced thrombocytopenia in hospitalized adults.","authors":"Ya Yang, Xiaogang Hu, Ya Ran, Hongqian Wang, Peishu Fu, Pengpeng Wan, Zhongqing Deng, Xiaoqin Lang, Ning Wang, Fengjun Sun, Yahan Fan, Yuntao Jia","doi":"10.1186/s40360-025-00874-7","DOIUrl":"10.1186/s40360-025-00874-7","url":null,"abstract":"<p><strong>Background: </strong>Linezolid (LZD) is used to treat infectious diseases caused by Gram-positive bacteria, but thrombocytopenia is one of the main adverse reactions to LZD administration. Early prediction of linezolid-induced thrombocytopenia (LI-TP) is of great importance to improve the clinical outcomes and prognoses. The aim of this study was to develop and validate a prediction model for LI-TP.</p><p><strong>Methods: </strong>A retrospective cohort of hospitalized adults receiving LZD therapy (January 2014-June 2022) was analyzed. Independent risk factors for LI-TP were identified via logistic regression in the training set (n = 757). A nomogram model for LI-TP were developed based on independent risk factors, and verified in validation set (n = 123).</p><p><strong>Results: </strong>The incidence of LI-TP was 13.5% (102/757). A logistic regression model was developed based on the seven independent risk factors, including age (≥ 60 y), duration of LZD therapy (> 11 d), bPLT (< 308 × 10⁹/L), ALT (> 100 IU/L), Ccr (< 67.5 mL/min), and concomitant use with VPA or Tac (p < 0.01) and transformed into a quantifiable nomogram. The nomogram demonstrated strong discrimination with AUCs of 0.760 in training (95% CI: 0.709-0.812, P < 0.001) and 0.767 in validation (95% CI: 0.635-0.899, P < 0.001). The calibration curves and Hosmer-Lemeshow tests confirmed good reliability and specificity of the nomogram model.</p><p><strong>Conclusion: </strong>This nomogram provides a practical tool for stratifying LI-TP risk, which provide an important reference for enabling timely clinical interventions to enhance LZD safety.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"47"},"PeriodicalIF":2.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522593","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":"Past use of metformin is associated with increased risk of myelodysplastic syndrome development in diabetes mellitus patients: a cross-sectional study of 54,869 patients.","authors":"Tamer Hellou, Guy Dumanis, Shir Portugez, Aviv Philip Goncharov, Eden Trodler, Asaf Stern, Imanuel Carlebach, Omer Kahlon, Maysan Abu Jwella, Ekram Nimer, Ahlam Athamna, Aya Berman, Gad Segal, Reut Kassif Lerner","doi":"10.1186/s40360-025-00882-7","DOIUrl":"10.1186/s40360-025-00882-7","url":null,"abstract":"<p><strong>Background: </strong>Myelodysplastic Syndrome (MDS) is a devastating hematologic malignancy associated with advanced age. Diabetes Mellitus (DM) is one of the most common morbidities worldwide, with metformin serving as the first line therapy for several decades. However, the potential association between previous metformin use and the risk of developing MDS remains uncertain.</p><p><strong>Methods: </strong>This cross-sectional study addressed the possible association between prior metformin use in DM patients and the subsequent development of MDS.</p><p><strong>Results: </strong>Data from 54,869 DM patients was retrieved from their medical records from a tertiary medical center. Of these, 20,318 patients had been exposed at some point in time to metformin, with 133 (0.7%) subsequently developing MDS. In contrast, among 34,551 DM patients with no prior exposure to metformin, only 154 (0.4%) developed MDS later in life. The Odds Ratio (OR) for MDS development amongst metformin users compared to the entire study population was 1.48 (95% CI 1.17-1.86; p = 0.001). A multivariate analysis adjusting for gender, age, congestive heart failure and chronic kidney disease, past exposure to metformin remained an independent risk factor for MDS development (OR = 1.6, 95% CI 1.26-2.03; p < 0.001).</p><p><strong>Conclusion: </strong>Previous exposure to metformin amongst DM patients is associated with an increased risk for MDS development later in life. This is a preliminary, cross-sectional study that show that larger studies in variable MDS patient populations are warranted.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"45"},"PeriodicalIF":2.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522684","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":"Haemorrhage-related adverse events profles of lenvatinib and pembrolizumab alone or in combination: a real-world pharmacovigilance study based on FAERS database.","authors":"Shiqiao Wang, Guizhi Ren, Heng Pan, Jiayi Chen, Jiayu Huang, Qinghua Mei, Zhongze Li, Guosheng Zou","doi":"10.1186/s40360-025-00878-3","DOIUrl":"10.1186/s40360-025-00878-3","url":null,"abstract":"<p><strong>Objective: </strong>Limited understanding exists regarding the haemorrhagic risk resulting from potential interactions between lenvatinib and pembrolizumab. We investigated haemorrhagic adverse events (ADEs) associated with co-administration of lenvatinib and pembrolizumab using data from the Food and Drug Administration Adverse Event Reporting System (FAERS) in an effort to provide recommendations for their safe and sensible use.</p><p><strong>Methods: </strong>The FAERS database's bleeding events linked to lenvatinib and pembrolizumab were carefully examined. Haemorrhagic signals mining was performed by the reported odds ratios (RORs) and information component (IC), corroborated by additive and multiplicative models.</p><p><strong>Results: </strong>A total of 38,416,055 adverse event cases were analyzed, with 1188 bleeding events records in the lenvatinib alone, 952 bleeding events records in the pembrolizumab alone and 420 bleeding events reports in the combination therapy, respectively. We observed a significantly higher risk of haemorrhage with the combination of lenvatinib and pembrolizumab compare with pembrolizumab alone. In addition, in the baseline model analysis of suspected bleeding adverse reactions, the additive model detected an increased incidence of small intestinal haemorrhage caused by combination therapy, and found no risk signals of tumour haemorrhage and tracheal haemorrhage; the results of multiplicative model are all negative.</p><p><strong>Conclusion: </strong>The analysis of FAERS data reveals different levels of haemorrhagic risk when lenvatinib and pembrolizumab are administered concurrently, highlighting the significance of being cautious when using them in clinical practice.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"44"},"PeriodicalIF":2.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143498887","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":"Real world results of ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia: a meta-analysis of clinical studies.","authors":"Mohammad Amin Karimi, Hanieh Norooziseyedhosseini, Reza Khademi, Alireza Ghajary, Haniyeh Kargar, Seyyedeh Sana Abdollahi, Mohaddeseh Belbasi, Mahdyieh Naziri, Niloofar Deravi, Sajjad Hajihosseini, Saharnaz Mofidi","doi":"10.1186/s40360-024-00832-9","DOIUrl":"10.1186/s40360-024-00832-9","url":null,"abstract":"<p><strong>Background: </strong>Chronic lymphocytic leukemia (CLL) is a B-cell malignancy primarily diagnosed in older adults. For younger patients, treatment options often include regimens based on fludarabine, cyclophosphamide, and rituximab; however, at least 20% of patients exhibit resistance to these therapies. Ibrutinib, a covalent Bruton's tyrosine kinase (BTK) inhibitor, has demonstrated enhanced safety compared to conventional treatments. This meta-analysis examines the efficacy and safety of ibrutinib in managing relapsed/refractory CLL.</p><p><strong>Method: </strong>Relevant keywords were used to conduct a comprehensive search across online databases, including PubMed, Scopus, and Google Scholar. Data related to complete response (CR), overall response rate (ORR), and adverse events were extracted to evaluate the efficacy and safety of ibrutinib treatment. The results were presented in forest plots illustrating event rates and risk ratios with 95% confidence intervals (CI), while heterogeneity was assessed using I² statistics. Funnel plots were employed to examine potential publication bias visually.</p><p><strong>Result: </strong>Twenty-one studies were included in this meta-analysis. Ibrutinib as a single-agent treatment was associated with a 9% complete response (CR) rate (95% CI: 5-14%) and a 77% overall response rate (ORR) (95% CI: 70-83%). When combined with other agents, ibrutinib achieved a CR rate of 21% (95% CI: 9-41%) and an ORR of 84% (95% CI: 80-88%). Adverse events were not significantly correlated with treatment outcomes. Funnel plots indicated no significant publication bias.</p><p><strong>Conclusion: </strong>Single-agent ibrutinib has proven to be an effective therapy for patients with relapsed/refractory CLL. However, combining ibrutinib with other agents has demonstrated enhanced treatment efficacy. Further studies are needed to evaluate the safety profile of this therapeutic regimen thoroughly.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"43"},"PeriodicalIF":2.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143498889","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":"Correction: Effects of cypermethrin exposure on learning and memory functions and anxiety-like behavior in rats.","authors":"Mansour Nazari, Mohammadmahdi Sabahi, Arash Salehipour, Sara Ami Ahmadi, Azin Kazemi, Shahab Razipour, Nafiseh Faraji, Alireza Komaki","doi":"10.1186/s40360-025-00876-5","DOIUrl":"10.1186/s40360-025-00876-5","url":null,"abstract":"","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"42"},"PeriodicalIF":2.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143498789","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}