BMC Pharmacology & Toxicology最新文献

{"title":"Mitigating hepatic ischemia and reperfusion injury with polyethylene glycol-enriched Ringer's lactate fluid: insights from an isolated perfused rat model.","authors":"Ikram Ben Jeddou, Mohamed Amine Zaouali, Roua Chaabani, Sameh Belgacem, Amira Cherif, Hassen Ben Abdennebi","doi":"10.1186/s40360-025-00835-0","DOIUrl":"10.1186/s40360-025-00835-0","url":null,"abstract":"<p><strong>Background: </strong>Cold ischemia-reperfusion (IR) injury is a multifactorial process detrimental to liver graft function during liver transplantation (LT). Although flushing hepatic grafts prior to reperfusion have been well explored, the optimal graft rinse solution to prevent cold IR injury remains largely undefined. The aim of this study was to evaluate whether a new rinse solution combining polyethylene glycol PM 35,000 Da (PEG35) with lactated solution (RLS) could mitigate cold IR injury in Wistar rats.</p><p><strong>Methods: </strong>Livers were isolated, preserved for 24 h and flushed immediately before ex vivo reperfusion with either RLS or PEG35-enriched RLS. Liver injury, graft function, energy balance, autophagy, oxidative stress as well as inflammatory response were assessed.</p><p><strong>Results: </strong>Flushing hepatic grafts with PEG35-enriched RLS resulted in decreased transaminase levels after cold ischemia. The improved graft function was evidenced by increased bile flow, enhanced BSP clearance, and reduced vascular resistance in these flushed grafts. Phospho-AMPK protein expression, as well as LC3B gene and protein expression were significantly increased compared to those unflushed and flushed only with RLS. PEG35-enriched RLS also maintained the oxidative state, as indicated by reduced activities of antioxidant enzymes and decreased MDA concentration. Additionally, this graft rinse solution down-regulated the inflammatory response by inhibiting the expression of genes involved in the HMGB-1/NF-κB/TNF-α signaling pathway.</p><p><strong>Conclusion: </strong>These data strongly suggest that rinsing liver grafts with PEG35-enriched RLS prior to reperfusion represents a simple and cost-effective strategy to enhance liver functional recovery after cold IR injury. This approach could serve as a viable alternative to RLS in clinical applications, highlighting the need for further research to explore its broader implications.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"70"},"PeriodicalIF":2.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717915","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":"Can quercetin reduce arsenic induced toxicity in mouse BALB/c 3T3 fibroblast cells? A study involving in vitro, molecular docking, and ADME predictions.","authors":"Velid Unsal, Cumali Keskin, Erkan Oner","doi":"10.1186/s40360-025-00906-2","DOIUrl":"10.1186/s40360-025-00906-2","url":null,"abstract":"<p><p>This study aimed to investigate the protective effect of quercetin against arsenic-induced oxidative damage, inflammation, and apoptosis in mouse BALB/c 3T3 fibroblast cells (NIH-3T3). Arsenic at different concentrations of 0.05 µM (low), 0.5 µM (medium), 10 µM (high) doses were used to induce toxicity, while 120 μm quercetin was used for treatment. MTT and LDH analyses were performed to determine the effect of arsenic and quercetin on cell viability, while oxidative stress markers and antioxidant enzyme activities were measured by spectrophotometric method. TNF-α and IL-1β levels were measured by the ELISA method, Autodock programs were used for molecular docking studies. In addition, computer-based analyses of quercetin and succimer molecules were performed using SwissADME web tools. TNF-α (PDB ID: 2AZ5), IL-1β (PDB ID: 1ITB), Caspase3 (PDB ID: 2XYG), Bax (PDB ID: 4S0O), SOD (PDB ID:1CBJ), GSH-Px (PDB ID: 1GP1) and Bcl-2 (PDB ID: 1G5M) crystal structures were obtained from the Protein Data Bank. Bax and Bcl-2 levels of apoptotic genes and mRNA expression levels of Caspase-3 activity were measured using the QRT-PCR technique. TUNEL staining was performed to determine DNA fragmentations, while DAPI staining was done to visualise nuclear modifications. Quercetin has been found to significantly reduce oxidative stress, inflammation, and apoptosis in cells and exert anti-apoptotic effects. Molecular docking studies revealed quercetin shows good binding affinity with molecules with SOD, GSH-Px, Bax, Bcl-2, Caspase-3, TNF-α and IL-1β structures, and has been observed to bind with Bax and Bcl-2 with molecular docking scores of -7.5 and - 7.7 kcal/mol, respectively. These findings are supported by results showing that quercetin is effective in anti-apoptotic and anti-inflammatory processes in arsenic-induced cells under in vitro conditions. In addition, when ADME values are examined, it can be considered that quercetin is a useful and effective candidate compound in reducing arsenic toxicity, considering its higher synthetic accessibility score, better pharmacokinetic properties, and good biological transition and interaction capacities compared to succimer.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"68"},"PeriodicalIF":2.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708340","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":"Combination of 10-hydroxy-decanoic acid and ZnO nanoparticles abrogates lead acetate-induced nephrotoxicity in rats: targeting oxidative stress and inflammatory signalling.","authors":"Samar R Saleh, Raheel G Agwah, Samar S Elblehi, Ahmed Z Ghareeb, Doaa A Ghareeb, Adham M Maher","doi":"10.1186/s40360-025-00888-1","DOIUrl":"10.1186/s40360-025-00888-1","url":null,"abstract":"<p><p>Lead is a heavy metal contaminant that can cause significant alterations in renal structure and function, resulting in nephrotoxicity. The fatty acids of royal jelly exhibit immunoregulatory, anticancer, anti-inflammatory, and antioxidant properties, which have garnered significant interest. The most prevalent among them is 10-hydroxydecanoic acid (10-HDA). Zinc oxide nanoparticles (ZnONPs) demonstrate a renoprotective effect, likely due to their antioxidant, anti-inflammatory, and antiapoptotic properties. This study evaluated the therapeutic efficacy of 10-HDA and ZnONPs, administered either as monotherapy or in combination, against lead-induced nephrotoxicity. Male rats were orally administered lead acetate (PbAc) for three months, followed by the administration of 10-HDA and/or ZnONPs for one month. Exposure to PbAc resulted in elevated renal lead concentration, as well as increased serum levels of urea, creatinine, and cystatin C. The condition resulted in damage to the renal parenchyma, characterised by degenerative glomeruli and tubules, and exhibited the highest lesion score. Nrf2 and HO-1 exhibited reduced expression and diminished antioxidant enzyme levels subsequent to PbAc poisoning. Additionally, there was an increase in the inflammatory and apoptotic signalling through the p-IKK/NF-κB axis. The administration of 10-HDA and ZnONPs significantly decreased renal lead levels and improved antioxidant capacity. Moreover, renal inflammatory markers (TNF-α, p-IKK, IL-1β, IL-6, and IL-8) and proapoptotic indicators (Bax and Caspase-3) were significantly suppressed. The combined therapy demonstrated a synergistic effect (combination index < 1). In conclusion, the results indicated that 10-HDA and ZnONPs have the potential to be a supplement or even an effective treatment to alleviate the adverse effects of lead poisoning. This is potentially attributed to their potent ameliorative actions against oxidation, inflammation, and apoptosis.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"69"},"PeriodicalIF":2.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708343","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":"Effects of adenosine triphosphate, thiamine pyrophosphate, melatonin, and liv-52 on subacute pyrazinamide proliferation hepatotoxicity in rats.","authors":"Sedat Ciftel, Serpil Ciftel, Durdu Altuner, Gulbaniz Huseynova, Nurinisa Yucel, Ali Sefa Mendil, Cengiz Sarigul, Halis Suleyman, Seval Bulut","doi":"10.1186/s40360-025-00901-7","DOIUrl":"10.1186/s40360-025-00901-7","url":null,"abstract":"<p><strong>Background: </strong>Hepatotoxicity of pyrazinamide, an antituberculosis drug, limits its therapeutic use and oxidative stress has been implicated in this toxicity. This study investigated the protective effects of adenosine triphosphate (ATP), thiamine pyrophosphate (TPP), melatonin, and Liv-52, which have previously been shown antioxidant activities, on pyrazinamide-induced hepatotoxicity.</p><p><strong>Methods: </strong>36 albino Wistar male rats were divided into randomized six groups; healthy (HG), pyrazinamide (PZG), ATP + pyrazinamide (APZG), TPP + pyrazinamide (TPZG), melatonin + pyrazinamide (MPZG) and Liv-52 + pyrazinamide (LPZG) groups. ATP 4 mg/kg and TPP 25 mg/kg were administered intraperitoneally (IP). Melatonin 10 mg/kg and Liv-52 20 mg/kg were given orally. One hour after administration of ATP, TPP, melatonin, and Liv-52, 250 mg/kg pyrazinamide was applied orally to all rats except HG group. The treatment was repeated (1 × 1) for 4 weeks. Then, blood samples were taken for determination of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Immediately after, the rats were euthanized with thiopental sodium (50 mg/kg, IP), and the livers were removed. The tissues were analyzed for malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) also hydropic degeneration, necrosis, and apoptosis (caspase 3) were examined.One-Way ANOVA was used in biochemical analyses and Tukey test was used as post-hoc. For histopathological and immunohistochemical analysis, the Kruskal-Wallis test was used and Dunn's test as a post-hoc.</p><p><strong>Results: </strong>Pyrazinamide increased MDA land decreased tGSH, SOD, and CAT levels in liver tissues (p < 0.001). It also increased serum ALT and AST activities and caused severe hydropic degeneration and necrosis in liver tissue (p < 0.001). ATP, TPP, melatonin, and Liv-52 significantly prevented the biochemical and histopathological changes induced by pyrazinamide (p < 0.05). On the other hand, Liv-52 was more successful than other potential protectors in protecting liver tissue from pyrazinamide damage (p < 0.05).</p><p><strong>Conclusions: </strong>ATP, TPP, melatonin, and Liv-52 can be used to protect liver tissue from pyrazinamide-induced hepatotoxicity in rats.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"67"},"PeriodicalIF":2.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699221","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":"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}