DARU Journal of Pharmaceutical Sciences最新文献

{"title":"Impact of concerning excipients on animal safety: insights for veterinary pharmacotherapy and regulatory considerations.","authors":"Vanessa Cola Thomazini, Gabriel Mendes da Cunha, Nayhara Madeira Guimarães, Soraya Dias Saleme, Rita Cristina Gonçalves de Melo, Geanne Aparecida de Paula, Suzana Gonçalves Carvalho, Marlus Chorilli, Cristiane Dos Santos Giuberti, Janaina Cecília Oliveira Villanova","doi":"10.1007/s40199-023-00486-8","DOIUrl":"10.1007/s40199-023-00486-8","url":null,"abstract":"<p><strong>Objectives: </strong>Veterinarians and pharmacists are familiar with the efficacy and safety aspects attributed to active pharmaceutical ingredients included in medicines, but they are rarely concerned with the safety of excipients present in medicines. Although generally recognized as safe, excipients are not chemically inert and may produce adverse events in certain animal populations. This review aims to present excipients of concern to these populations and highlight their relevance for rational veterinary pharmacotherapy.</p><p><strong>Evidence acquisition: </strong>A comprehensive review of the literature about the existence of adverse reactions in animals caused by pharmaceutical excipients was carried out based on an exploratory study. An overview of the correct conditions of use and safety of these excipients has also been provided, with information about their function, the proportion in which they are included in the different pharmaceutical dosage forms and the usual routes of administration.</p><p><strong>Results: </strong>We identified 18 excipients considered of concern due to their potential to cause harm to the health of specific animal populations: bentonite, benzalkonium chloride, benzoic acid, benzyl alcohol, ethanol, lactose, mannitol, mineral oil, monosodium glutamate, polyethylene glycol, polysorbate, propylene glycol, sodium benzoate, sodium carboxymethylcellulose, sodium lauryl sulfate, sulfites, polyoxyethylene castor oil derivatives, and xylitol. Among the 135 manuscripts listed, only 24 referred to studies in which the substances were correctly evaluated as excipients.</p><p><strong>Conclusions: </strong>Based on the information presented in this review, the authors hope to draw the attention of professionals involved in veterinary pharmacotherapy to the existence of excipients of concern in medicines. This information contributes to rational veterinary pharmacotherapy and supports veterinary pharmacovigilance actions. We hope to shed light on the subject and encourage studies and new manuscripts that address the safety of pharmaceutical excipients to the animal population.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"289-305"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71411061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrochemical evaluation of nivolumab used in cancer treatment with differential pulse voltammetry: A novel approach with single-use pencil graphite electrode.","authors":"Mehmet Aslan, Fırat Aydın, Abdulkadir Levent","doi":"10.1007/s40199-023-00491-x","DOIUrl":"10.1007/s40199-023-00491-x","url":null,"abstract":"<p><strong>Objectives: </strong>Nivolumab is used in a treatment called immunotherapy, which helps the immune system cells to attack cancer cells. The electrochemical properties and quantification of this drug were performed using single-use pencil tips.</p><p><strong>Evidence acquisition: </strong>Here, a selective voltammetric method for the determination and electrochemical characterization of Nivolumab used in cancer therapy was developed for the first time using a disposable pencil electrode by cyclic voltammetry and differential pulse voltammetry techniques. Nivolumab exhibited an anodic signal at +0.879 V (vs. Ag/AgCl) in PBS (pH 3.0, 0.02 M NaCl) medium.</p><p><strong>Results: </strong>This procedure showed a linear response in phosphate buffer solutions (pH 3.0, 0.02 M NaCl) media within the concentration range of 0.01 mg mL^-1 to 0.07 mg mL^-1 and limit of detection and the limit of quantification values were determined to be 2.49 μg mL^-1 and 8.30 μg mL^-1, respectively.</p><p><strong>Conclusions: </strong>The developed method offers an important analytical approach for the detection and characterization of NIVO. Precisely measuring and monitoring the levels of such drugs in real sample analyses or biological samples is critical for evaluating response to treatment, optimizing treatment strategies. Therefore, the method was applied to real sample analyses. Voltammetric results developed using PG electrode were compared with UV-Vis results. It has been determined that the results obtained are compatible with each other.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"109-120"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138290598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Towards greater impact in health technology assessment: System dynamic approach for new and emerging technologies in Iran.","authors":"Zahra Goudarzi, Milad Ahmadi Marzaleh, Shekoufeh Nikfar, Abbas Kebriaeezadeh, Reza Yousefi Zenouz, Akbar Abdollahiasl, Mojtaba Nouhi","doi":"10.1007/s40199-023-00483-x","DOIUrl":"10.1007/s40199-023-00483-x","url":null,"abstract":"<p><strong>Purpose: </strong>As classical health technology assessment models fail to predict the complexities of related impacts, the application of modeling techniques such as systems dynamics simulation (SD) is essential. This study aimed to develop an SD model to predict the outcomes of access to a new medicine in Iran.</p><p><strong>Methods: </strong>This study extracted the important and influential variables in providing access to new pharmaceutical technologies by comprehensively reviewing previous research and combining the technical knowledge of experts in this field. The variables were incorporated into the systems thinking framework and modeled using dynamic systems tools, followed by simulation and testing in VENSIM. The model was piloted for deferoxamine and deferasirox in thalassemia. Various tests were used to evaluate the validity and reliability of the model. The model was designed for a ten-year horizon (2018-2028) for medicines selected as the pilot.</p><p><strong>Results: </strong>The variables extracted from the panel of experts encompassed the primary and short-term impacts of access to newly emerged medicine and long-term impacts regarding the economy, health, and society. After modeling, the leverage points presented for the problem with the greatest impact or effectiveness in access to new medicine included the policy determining the amount of medicine supply, the import and production of medicine, the prevalence and incidence of disease, insurance coverage, and treatment adherence.</p><p><strong>Conclusion: </strong>The SD models allow the researchers to evaluate the efficiency and health outcomes of a new pharmaceutical more precisely in the health system in Iran.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"25-45"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71421480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational Screening Using a Combination of Ligand-Based Machine Learning and Molecular Docking Methods for the Repurposing of Antivirals Targeting the SARS-CoV-2 Main Protease.","authors":"Gusti Putu Wahyunanda Crista Yuda, Naufa Hanif, Adam Hermawan","doi":"10.1007/s40199-023-00484-w","DOIUrl":"10.1007/s40199-023-00484-w","url":null,"abstract":"<p><strong>Background: </strong>COVID-19 is an infectious disease caused by SARS-CoV-2, a close relative of SARS-CoV. Several studies have searched for COVID-19 therapies. The topics of these works ranged from vaccine discovery to natural products targeting the SARS-CoV-2 main protease (M^pro), a potential therapeutic target due to its essential role in replication and conserved sequences. However, published research on this target is limited, presenting an opportunity for drug discovery and development.</p><p><strong>Method: </strong>This study aims to repurpose 10692 drugs in DrugBank by using ligand-based virtual screening (LBVS) machine learning (ML) with Konstanz Information Miner (KNIME) to seek potential therapeutics based on M^pro inhibitors. The top candidate compounds, the native ligand (GC-376) of the M^pro inhibitor, and the positive control boceprevir were then subjected to absorption, distribution, metabolism, excretion, and toxicity (ADMET) characterization, drug-likeness prediction, and molecular docking (MD). Protein-protein interaction (PPI) network analysis was added to provide accurate information about the M^pro regulatory network.</p><p><strong>Results: </strong>This study identified 3,166 compound candidates inhibiting M^pro. The random forest (RF) molecular access system ML model provided the highest confidence score of 0.95 (bromo-7-nitroindazole) and identified the top 22 candidate compounds. Subjecting the 22 candidate compounds, the native ligand GC-376, and boceprevir to further ADMET property characterization and drug-likeness predictions revealed that one compound had two violations of Lipinski's rule. Additional MD results showed that only five compounds had more negative binding energies than the native ligand (- 12.25 kcal/mol). Among these compounds, CCX-140 exhibited the lowest score of - 13.64 kcal/mol. Through literature analysis, six compound classes with potential activity for M^pro were discovered. They included benzopyrazole, azole, pyrazolopyrimidine, carboxylic acids and derivatives, benzene and substituted derivatives, and diazine. Four pathologies were also discovered on the basis of the M^pro PPI network.</p><p><strong>Conclusion: </strong>Results demonstrated the efficiency of LBVS combined with MD. This combined strategy provided positive evidence showing that the top screened drugs, including CCX-140, which had the lowest MD score, can be reasonably advanced to the in vitro phase. This combined method may accelerate the discovery of therapies for novel or orphan diseases from existing drugs.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"47-65"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71421478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimicrobial activity and mechanism of anti-MRSA of phloroglucinol derivatives.","authors":"Xianjing Yang, Xinjiao Gao, Jiayi Ou, Gong Chen, Lianbao Ye","doi":"10.1007/s40199-024-00503-4","DOIUrl":"10.1007/s40199-024-00503-4","url":null,"abstract":"<p><strong>Background: </strong>In previous studies, authors have completed the total synthesis of several phloroglucinol natural products and synthesized a series of their derivatives, which were tested with good biological activities.</p><p><strong>Objectives: </strong>To discover anti-MRSA lead compound and study their mechanism of action.</p><p><strong>Methods: </strong>Phloroglucinol derivatives were tested to investigate their activities against several gram-positive strains including Methicillin-resistant Staphylococcus aureus (MRSA). The mechanism study was conducted by determining extracellular potassium ion concentration, intracellular NADPH oxidase content, SOD activity, ROS amount in MRSA and MRSA survival rate under A5 treatment. The in vitro cytotoxicity test of A5 was conducted.</p><p><strong>Results: </strong>The activity of monocyclic compounds was stronger than that of bicyclic compounds, and compound A5 showed the best MIC value of 0.98 μg/mL and MBC value of 1.95 μg/mL, which were 4-8 times lower than that of vancomycin. The mechanism study of A5 showed that it achieved anti-MRSA effect through membrane damage, which is proved by increased concentration of extracellular potassium ion after A5 treatment. Another possible mechanism is the over ROS production induced cell death, which is suggested by observed alternation of several reactive oxygen species (ROS) related indicators including NADPH concentration, superoxide dismutase (SOD) activity, ROS content and bacterial survival rate after A5 treatment. The cytotoxicity results in vitro showed that A5 was basically non-toxic to cells.</p><p><strong>Conclusion: </strong>Acylphloroglucinol derivative A5 showed good anti-MRSA activity, possibly via membrane damage and ROS-mediated oxidative stress mechanism. It deserves further exploration to be a potential lead for the development of new anti-MRSA agent.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"177-187"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Educational interventions in pharmacovigilance to improve the knowledge, attitude and the report of adverse drug reactions in healthcare professionals: Systematic Review and Meta-analysis.","authors":"Mónica J Cervantes-Arellano, Osvaldo D Castelán-Martínez, Yolanda Marín-Campos, Juan L Chávez-Pacheco, Olga Morales-Ríos, Laura M Ubaldo-Reyes","doi":"10.1007/s40199-024-00508-z","DOIUrl":"10.1007/s40199-024-00508-z","url":null,"abstract":"<p><strong>Objectives: </strong>Underreporting of adverse drug reactions (ADRs) limits and delays the detection of signs. The aim of this systematic review with meta-analyses was to synthesize the evidence of educational interventions (EIs) efficacy in health professionals to increase ADR reporting, attitudes, and knowledge of pharmacovigilance.</p><p><strong>Evidence acquisition: </strong>A systematic literature review was carried out to identify randomized clinical trials evaluating the efficacy of EI in pharmacovigilance in health professionals to improve ADR reports, knowledge, and attitude toward pharmacovigilance. ADR reports were pooled by calculating Odds Ratio (OR) with a 95% confidence interval (95%CI), while pharmacovigilance knowledge and attitude were pooled by calculating a mean difference (MD) with 95%CI. In addition, the subanalysis was performed by EI type. Meta-analysis was performed with RevMan 5.4 software. PROSPERO registry CRD42021254270.</p><p><strong>Results: </strong>Eight hundred seventy-five articles were identified as potentially relevant, and 11 were included in the systematic review. Metanalysis showed that EI increased ADR reporting in comparison with control group (OR = 4.74, [95%CI, 2.46 to 9.12], I² = 93%, 5 studies). In subgroup analysis, the workshops (OR = 6.26, [95%CI, 4.03 to 9.73], I² = 57%, 3 studies) increased ADR reporting more than telephone-based interventions (OR = 2.59, [95%CI, 0.77 to 8.73], I² = 29%, 2 studies) or combined interventions (OR = 5.14, [95%CI, 0.97 to 27.26], I² = 93%, 3 studies). No difference was observed in pharmacovigilance knowledge. However, the subanalysis revealed that workshops increase pharmacovigilance knowledge (SMD = 1.85 [95%CI, 1.44 to 2.27], 1 study). Only one study evaluated ADR reporting attitude among participants and showed a positive effect after the intervention.</p><p><strong>Conclusion: </strong>EI improves ADR reports and increases pharmacovigilance knowledge. Workshops are the most effective EI to increase ADR reporting.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"421-434"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139995883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immediate hypersensitivity reaction to levetiracetam: a case report study.","authors":"Mahnaz Sadat Hosseini, Soha Namazi","doi":"10.1007/s40199-023-00488-6","DOIUrl":"10.1007/s40199-023-00488-6","url":null,"abstract":"<p><strong>Background: </strong>Anticonvulsant drugs are one of the most common causes of delayed hypersensitivity reactions, such as drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). These reactions are more prevalent with aromatic anticonvulsant drugs such as phenytoin and carbamazepine. However, immediate hypersensitivity reactions such as urticaria, angioedema, and anaphylaxis with anticonvulsant drugs are rare. We describe a 51-year-old woman who developed spreading skin rashes on her wrists with urticaria and pruritus 24 h after receiving intravenous levetiracetam.</p><p><strong>Conclusion: </strong>Clinicians should be aware of immediate hypersensitivity reactions with intravenous levetiracetam.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"435-438"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71421479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fruit vinegar as a promising source of natural anti-inflammatory agents: an up-to-date review.","authors":"Driss Ousaaid, Meryem Bakour, Hassan Laaroussi, Asmae El Ghouizi, Badiaa Lyoussi, Ilham El Arabi","doi":"10.1007/s40199-023-00493-9","DOIUrl":"10.1007/s40199-023-00493-9","url":null,"abstract":"<p><strong>Objectives: </strong>Fruit vinegar is one of the most famous fruit byproducts worldwide with several unique properties. There are two types of fruit vinegar, artisanal and industrial, for consumers to choose from. This review aims to assess for the first time the phytochemistry of fruit vinegar and its anti-inflammatory effects.</p><p><strong>Method: </strong>The present work was conducted based on a literature search that selected the relevant papers from indexed databases such as Scopus, Science Direct, MDPI, PubMed, Hindawi, and Web of Science. We used numerous terms to assure a good search in different databases, including fruit vinegar, phytochemistry, bioavailability and bioaccessibility, and anti-inflammatory effect. All articles were selected based on their relevance, quality, and problematic treatment.</p><p><strong>Results: </strong>Literature data have shown that vinegar has a long medicinal history and has been widely used by different civilizations, due to its richness in bioactive molecules, vinegar plays an important role in the prevention and treatment of various inflammatory diseases, including atopic dermatitis, mastitis, asthma, arthritis, acute pancreatitis, and colitis. Fruit vinegar consumption benefit is highly dependent on its chemical composition, especially organic acids and antioxidants, which can act as nutraceuticals.</p><p><strong>Conclusion: </strong>Fruit vinegar has a rich chemical composition, including organic acids that can be transformed in the digestive system into compounds that play an important role in health-promoting features such as anti-inflammatory effects throughout the control of intestinal microbiota and pro-inflammatory cytokine production.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"307-317"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138470079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of 1,10-phenanthroline-based hydroxamate derivative as dual histone deacetylases/ribonucleotide reductase inhibitor with antitumor activities","authors":"Manasa Gangadhar Shetty, Padmini Pai, Bipasa Dey, Kapaettu Satyamoorthy, Suranjan Shil, Usha Yogendra Nayak, Ashwini T, Babitha Kampa Sundara","doi":"10.1007/s40199-024-00514-1","DOIUrl":"https://doi.org/10.1007/s40199-024-00514-1","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Aberrant expression of histone deacetylases (HDACs) and ribonucleotide reductase (RR) enzymes are commonly observed in various cancers. Researchers are focusing on these enzymes in cancer studies with the aim of developing effective chemotherapeutic drugs for cancer treatment. Targeting both HDAC and RR simultaneously with a dual HDAC/RR inhibitor has exhibited enhanced effectiveness compared to monotherapy in cancer treatment, making it a promising strategy.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>The objective of the study is to synthesize and assess the anti-cancer properties of a 1,10-phenanthroline-based hydroxamate derivative, characterizing it as a novel dual HDAC/RR inhibitor.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>The <i>N</i>¹-hydroxy-<i>N</i>⁸-(1,10-phenanthrolin-5-yl)octanediamide (PA), a 1,10-phenanthroline-based hydroxamate derivative, was synthesized and structurally characterized. The compound was subjected to in vitro assessments of its anti-cancer, HDAC, and RR inhibitory activities. In silico docking and molecular dynamics simulations were further studied to explore its interactions with HDACs and RRM2.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The structurally confirmed PA exhibited antiproliferative activity in SiHa cells with an IC₅₀ of 16.43 μM. It displayed potent inhibitory activity against HDAC and RR with IC₅₀ values of 10.80 μM and 9.34 μM, respectively. Co-inhibition of HDAC and RR resulted in apoptosis-induced cell death in SiHa cells, mediated by the accumulation of reactive oxygen species (ROS). In silico docking studies demonstrated that PA can effectively bind to the active sites of HDAC isoforms and RRM2. Furthermore, PA demonstrated a more favorable interaction with HDAC7, displaying a docking score of -9.633 kcal/mol, as compared to the standard HDAC inhibitor suberoylanilide hydroxamic acid (SAHA), which exhibited a docking score of -8.244 kcal/mol against HDAC7.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The present study emphasizes the prospect of designing a potential 1,10-phenanthroline hydroxamic acid derivative as a novel dual HDAC and RR-inhibiting anti-cancer molecule.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"30 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140812827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of time-to-onset and outcome of cardiac adverse events related to pembrolizumab using post-marketing surveillance in Japanese patients","authors":"Yuko Kanbayashi, Eren Tsuchiya, Tadashi Shimizu, Mayako Uchida","doi":"10.1007/s40199-024-00516-z","DOIUrl":"https://doi.org/10.1007/s40199-024-00516-z","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Pembrolizumab has been widely used in patients since its release, but information on cardiac Adverse Events (AEs) related to pembrolizumab remains lacking, particularly in Japanese populations.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>This study aims to evaluate time to onset, incidence rates, and outcomes for pembrolizumab-induced cardiac AEs in patients with cancer using the Japanese Adverse Drug Event Report database.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We analysed data for the period from April 2004 to March 2022. Data on cardiac AEs were extracted and relative risks of AEs were estimated using the reporting odds ratio.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>We analysed 2,021,907 reports and identified 15,306 reports of AEs caused by pembrolizumab. Of these, 399 cardiac AEs were associated with pembrolizumab. Signals were detected for six cardiac AEs: myocarditis, immune-mediated myocarditis, pericardial effusion, cardiac tamponade, pericarditis, and pericarditis malignant. A histogram of median times to onset showed occurrence from 33 (21–97) days for immune-mediated myocarditis to 138 (67–168) days for pericarditis malignant, but some cases occurred even more than 1 year after the start of administration. Among these, myocarditis was the most frequently reported (27.1%), with fatal cases also reported.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>This study focused on cardiac AEs caused by pembrolizumab as post-marketing AEs. Patients should be monitored not only at the time of administration, but also over time for signs of these AEs, especially myocarditis, as some patients may have serious outcomes.</p><h3 data-test=\"abstract-sub-heading\">Graphical abstract</h3>\u0000","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"14 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140804998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}