BMC Pharmacology & Toxicology最新文献

{"title":"A study on the pharmacokinetic bioequivalence of oral tablet formulations of riluzole among healthy volunteers utilizing HPLC-MS/MS.","authors":"Fei Yu, Rui Wang, Keli Wang, BoYang Lin, Xuan Zhou, Linghong Chen, Li Ma, Zheng Liao, Wanggang Zhang","doi":"10.1186/s40360-025-00931-1","DOIUrl":"10.1186/s40360-025-00931-1","url":null,"abstract":"<p><strong>Introduction: </strong>This randomized, open-label, two period, two treatment, fasting bioequivalence trial was conducted to demonstrate the bioequivalence between riluzole tablets manufactured by Jiangsu Enhua Pharmaceutical Co., Ltd. and the reference preparations from Sanofi Winthrop Industry (certified by Sanofi Mature IP) in healthy individuals.</p><p><strong>Objective: </strong>The study aimed to compare the pharmacokinetic parameters and evaluate the bioequivalence of both preparations when taken on an empty stomach. Additionally, the safety profile of both preparations was assessed in the study population.</p><p><strong>Methods: </strong>Seventy-two subjects participated in the trial and received riluzole tablets once per dosing cycle while fasting. They were randomLy assigned to either a 50-mg test or reference formulation, with a 7-day washout period between cycles. Venous blood samples (4 mL) were collected 22 times from each subject, starting before dosing (0 h) and ending 48 h after. Plasma riluzole concentrations were measured using liquid chromatography tandem mass spectrometry. This clinical trial has been officially registered in the Chinese Clinical Trial Register (accessible at http://www.chinadrugtrials.org.cn/index.htmL ) with the registration number CTR20230637 on March 02, 2023.</p><p><strong>Results: </strong>The results showed that the geometric mean ratios of key pharmacokinetic parameters-including the area under the plasma concentration-time curve from time zero to the last nonzero concentration (AUC_0 - t) (102.21%; confidence interval [CI], 96.85-107.86%), AUC from time zero to infinity (AUC_0-∞) (102.03%; CI, 96.86-107.47%), and the peak plasma concentration (C_max) (107.47%; CI, 95.03-121.54%)-all fell within the bioequivalence acceptance range of 80-125%. Importantly, no serious adverse events were reported, and no subjects withdrew due to adverse events, indicating good tolerability of both formulations among the healthy Chinese volunteers.</p><p><strong>Conclusion: </strong>These findings establish the bioequivalence of the 50-mg test preparation of oral riluzole tablets with the reference listed drug.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"105"},"PeriodicalIF":2.8,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075936","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":"Prevalence and clinical significance of potential drug-drug interactions of antimicrobials in Intensive Care Unit patients: a retrospective study.","authors":"Shanshan Xu, Zhihui Song, Jie Bai, Jiawei Wang","doi":"10.1186/s40360-025-00925-z","DOIUrl":"https://doi.org/10.1186/s40360-025-00925-z","url":null,"abstract":"<p><strong>Background: </strong>Antimicrobials are frequently prescribed in Intensive Care Units (ICUs), where drug-drug interactions (DDIs) with other medications may exacerbate clinical outcomes. Limited evidence exists on the prevalence and clinical impact of these interactions.</p><p><strong>Objective: </strong>To estimate the prevalence of potential DDIs (pDDIs) between antimicrobials and other drugs in ICU patients using two electronic DDIs databases, identify the actual DDIs and the most frequently implicated antimicrobials, and determine the risk factors associated with actual DDIs.</p><p><strong>Methods: </strong>We conducted a retrospective study on patients admitted to intensive care units from January to December 2023. Micromedex and Lexi-Interact were used to identify pDDIs and their severities. Furthermore, we used the Drug Interaction Probability Scale (DIPS) criteria to identify actual DDIs.</p><p><strong>Results: </strong>Among 2,154 patients, 2,163 pDDIs (108 unique pairs) were identified in 461 patients, and 2.87% (62 pDDIs in 46 patients) were classified as actual DDIs. The antimicrobials most likely to cause pDDIs included quinolones, triazole antifungals, and linezolid. Antimicrobial-drug pairs with a higher incidence of severe pDDIs included linezolid-dopamine/metoclopramide (hypertension), voriconazole-budesonide for inhalation (increased serum concentration of budesonide), and levofloxacin-amiodarone (QT prolongation). The antimicrobial-drug pairs with a higher occurrence of actual DDIs included linezolid-dopamine/dobutamine (hypertension), fluconazole-amiodarone/ritonavir (QT prolongation), and cefoperazone/vancomycin-furosemide (nephrotoxicity). Moderate agreement existed between the two databases for pDDIs detection (Cohen's kappa = 0.546), but severity ratings diverged. Multivariable analysis identified the number of drugs per patient (OR = 1.178, p < 0.001), the number of antimicrobials per patient (OR = 1.146, p < 0.038), and the length of stay in the ICU (OR = 1.093, p < 0.038) as significant risk factors.</p><p><strong>Conclusions: </strong>High pDDI rates involving antimicrobials were observed in ICU patients, though actual DDIs were infrequent. Notable severe risk pairs warrant vigilant monitoring, especially with a higher occurrence of actual DDIs. Discrepancies in DDI databases emphasize the need for multi-tool validation to optimize medication safety.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"104"},"PeriodicalIF":2.8,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075951","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":"In-situ gel bases ocular delivery system of Ganciclovir, in-vivo and in-vitro investigation.","authors":"Susanta Paul, Subhabrota Majumdar, Mainak Chakraborty, Swarupananda Mukherjee, Nilanjan Sarkar, Bhupendra Prajapati, Nemat Ali, Abdullah F AlAsmari, Shamama Nishat","doi":"10.1186/s40360-025-00934-y","DOIUrl":"10.1186/s40360-025-00934-y","url":null,"abstract":"<p><p>Ocular drug delivery is challenging due to the eye's unique anatomy and physiology, which limit drug absorption and distribution. Traditional methods like eye drops have poor bioavailability and often require frequent dosing. In-situ gel systems, liquid formulations that transform into a gel upon contact with physiological conditions (pH, temperature, or ions in tear fluid), offer several advantages for ocular drug delivery. Ganciclovir was incorporated into a thermoresponsive in situ gel base. Nine formulations were prepared using the cold technique and a 3² full factorial design. The physical properties of ganciclovir gel, including clarity, pH, viscosity, gelation temperature, and gelation time, were scrutinized. In vitro drug release was assessed using a dialysis membrane method, and ocular toxicity was evaluated in a rabbit model. Poloxamer 407 and HPMC E-50 LV were used to prepare the gel, with the 3² factorial design analyzing the effects of varying concentrations on the gel's viscosity, gelation temperature, and gelation time. The optimized in-situ gel formulation (Batch B5) contained 15% w/v poloxamer 407 and 1% w/v HPMC E-50 LV, achieving a viscosity of 64.81 cPs, with a gelation temperature of 39.0 °C and a gelation time of 183 s. This formulation demonstrated better permeability and sustained ganciclovir release than a commercial formulation. Ocular toxicity studies confirmed that the formulation was non-irritating and well-tolerated. Overall, the gel showed suitable physical properties, sustained drug release over 12 h, and significant potential for enhancing drug bioavailability and treatment efficacy for ocular infections. These findings confirm that the optimized ganciclovir in situ gel preparation improves eye permeation and prolongs ocular retention time, thus enhancing its therapeutic efficacy. Its sustained release and prolonged retention time make it a promising alternative to conventional eye drops, offering better patient compliance and efficacy.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"102"},"PeriodicalIF":2.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963270","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":"Identifying Lactylation-related biomarkers and therapeutic drugs in ulcerative colitis: insights from machine learning and molecular docking.","authors":"Yao Yang, Xu Sun, Bin Liu, Yunshu Zhang, Tong Xie, Junchen Li, Jifeng Liu, Qingkai Zhang","doi":"10.1186/s40360-025-00939-7","DOIUrl":"10.1186/s40360-025-00939-7","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis (UC), a chronic relapsing-remitting inflammatory bowel disease. Recent studies have shown that lactylation modifications may be involved in metabolic-immune interactions in intestinal inflammation through epigenetic regulation, but their specific mechanisms in UC still require in-depth validation.</p><p><strong>Methods: </strong>We conducted comparative analyses of transcriptomic profiles, immune landscapes, and functional pathways between UC and normal cohorts. Lactylation-related differentially expressed genes were subjected to enrichment analysis to delineate their mechanistic roles in UC. Through machine learning algorithms, the diagnostic model was established. Further elucidating the mechanisms and regulatory network of the model gene in UC were GSVA, immunological correlation analysis, transcription factor prediction, immunofluorescence, and single-cell analysis. Lastly, the CMap database and molecular docking technology were used to investigate possible treatment drugs for UC.</p><p><strong>Results: </strong>Twenty-two lactylation-related differentially expressed genes were identified, predominantly enriched in actin cytoskeleton organization and JAK-STAT signaling. By utilizing machine learning methods, 3 model genes (S100A11, IFI16, and HSDL2) were identified. ROC curves from the train and test cohorts illustrate the superior diagnostic value of our model. Further comprehensive bioinformatics analyses revealed that these three core genes may be involved in the development of UC by regulating the metabolic and immune microenvironment. Finally, regorafenib and R-428 were considered as possible agents for the treatment of UC.</p><p><strong>Conclusion: </strong>This study offers a novel strategy to early UC diagnosis and treatment by thoroughly characterizing lactylation modifications in UC.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"103"},"PeriodicalIF":2.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957125","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":"Predictive role of cystatin C and increased proteinuria in early assessment of acute renal toxicity in patient poisoned by nephrotoxic drugs and poisons.","authors":"Esam Mohammed Abdallah Ali, Emad Ahmad Mohamad Yousef, Maha Abd El-Hamed Helal, Mohammed Hamdi Mohammed, Meray Medhat Shokry Zaghary, Marwa Ahmed Hasb Elnabi","doi":"10.1186/s40360-025-00935-x","DOIUrl":"10.1186/s40360-025-00935-x","url":null,"abstract":"<p><strong>Background: </strong>Acute kidney injury (AKI) is prevalent in critical care, often due to nephrotoxic drug exposure, which accounts for significant morbidity and mortality. Current biomarkers, like serum creatinine, lack sensitivity for early detection of nephrotoxicity.</p><p><strong>Aim: </strong>This study evaluates proteinuria and serum cystatin C as early indicators of nephrotoxicity in acutely poisoned patients at Sohag University Hospitals.</p><p><strong>Methods: </strong>This prospective study involved 100 acutely poisoned patients with nephrotoxic effects admitted to Sohag University Hospitals from April to August 2021. Inclusion criteria required symptomatic patients who provided at least four blood or urine samples, including one within 24 h post-ingestion. AKI was classified using the Acute Kidney Injury Network (AKIN) criteria, with baseline serum creatinine estimated from the lowest value during hospitalization. Biomarkers, including serum creatinine and cystatin C, were measured using standard assays for analysis.</p><p><strong>Results: </strong>The study included 100 patients aged 2 to 58 years, predominantly male (72%). Most participants were from rural areas (82%). Serum creatinine levels significantly increased from day 1 (mean ± SD: 1.67 ± 0.6 mg/dL) to day 2 (mean ± SD: 2.98 ± 1.35 mg/dL). Significant predictors of acute renal toxicity included serum creatinine on both days (P < 0.001), proteinuria ACR (P = 0.023), and cystatin C (P < 0.001). Cystatin C had the highest predictive value (AUC = 0.993), while proteinuria ACR and day 2 serum creatinine showed significant predictive capabilities (AUCs of 0.805 and 0.873, respectively).</p><p><strong>Conclusion: </strong>In conclusion, proteinuria and cystatin C are reliable predictors for early nephrotoxicity detection in acutely poisoned patients at Sohag University Hospitals. These biomarkers effectively indicate and assess the severity of kidney injury caused by toxicity.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"101"},"PeriodicalIF":2.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975182","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":"Melatonin enhances everolimus efficacy in breast cancer by suppressing mTOR pathway activation and promoting apoptosis and mitochondrial function.","authors":"Şeyma Demirkesen, Yakup İriağaç, Erdoğan Selçuk Şeber, Cenk Aral","doi":"10.1186/s40360-025-00907-1","DOIUrl":"10.1186/s40360-025-00907-1","url":null,"abstract":"<p><strong>Background: </strong>Everolimus is used in the treatment of breast cancer by targeting the PI3K/AKT/mTOR pathway, particularly during anti-hormonal therapy. The efficacy of everolimus is limited due to a feedback loop that supresses mTOR while simultaneously enhancing Akt activation in endocrine-resistant breast cancer. Melatonin (N-acetyl-5-methoxytryptamine) regulates mitochondrial activity, cell death, and autophagy due to its strong free radical scavenging, antioxidant, and anti-inflammatory characteristics. Melatonin, a naturally occurring oncostatic agent, slows tumor growth in a range of malignancies, including breast cancer. Due to its ability to protect healthy cells from oxidative stress and inflammation, along with its anti-cancer properties, melatonin has the potential to serve asan effective adjuvant in breast cancer therapy. It also inhibits the phosphorylation of mTOR and Akt, two essential pathways implicated in breast cancer growth, which may aid in overcoming resistance to targeted treatments like everolimus. The combination effects of melatonin and everolimus on hormone receptor-positive breast cancer remains unexplored. This study examined the effectiveness of melatonin when combined with everolimus for the treatment of hormone receptor-positive breast cancer.</p><p><strong>Methods: </strong>To investigate the effects of melatonin and everolimus combination, we divided MCF-7 cells into four experimental groups: the control, Melatonin (3 mM), Everolimus (30 nM), and a combination of Melatonin and Everolimus (3 mM + 30 nM). Cell viability, apoptosis, autophagy activation, and mitochondrial function were evaluated using established techniques.</p><p><strong>Results: </strong>Based on the cell viability test, the combination of 30 nM everolimus and 3 mM melatonin inhibited phosphorylation of 4E-BP1 and p70S6K, which are downstream effectors of the mTOR pathway, and reduced cell growth. In addition, co-administration of melatonin and everolimus increased apoptosis and led to Sub-G1 phase accumulation. LC3 protein expression and LC3 puncta analysis demonstrated autophagic activity. In terms of mitochondrial function, co-administration of melatonin with everolimus did not cause proton leakage or mitochondrial uncoupling, but did restore everolimus-induced respiratory inhibition.</p><p><strong>Conclusions: </strong>In conclusion, melatonin is thought to improve the effectiveness of everolimus by inhibiting mTOR downstream effectors, enhancing apoptosis, activating autophagy, improving mitochondrial respiration, and reducing MCF-7 growth.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"100"},"PeriodicalIF":2.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970120","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":"The safety, tolerability, pharmacokinetics, and pharmacodynamics of nebulized pegylated interferon α-2b in healthy adults: a randomized phase 1 trial.","authors":"Wenqi Huang, Yanneng Kang, Yajun Zhao, Jiao Yang, Changjuan Dai, Weibing Wu, Jinchao Xu, Wen Jin, Xiaolu Wu, Qing Zhou","doi":"10.1186/s40360-025-00937-9","DOIUrl":"10.1186/s40360-025-00937-9","url":null,"abstract":"<p><strong>Background: </strong>Interferons (IFNs) are proteins that combat viruses and regulate the immune system. Studies have demonstrated that aerosol inhalation of IFNα is both effective and safe for treating respiratory infections. However, IFNα has a short half-life and is rapidly cleared by lung defenses. Polyethylene glycol (PEG) ylation is a common strategy to extend the duration of drug action. PegIFNα-2b is a long-acting interferon formed by the covalent binding of 40 kDa Y-shaped branched PEG with recombinant human IFNα-2b. This study aimed to assess the safety, tolerability, pharmacokinetic, and pharmacodynamic characteristics of nebulized PegIFNα-2b in healthy adult subjects, providing guidance for further clinical investigations.</p><p><strong>Methods: </strong>This study employed a randomized, controlled clinical trial design with a total of 18 healthy adult subjects enrolled. Participants were randomly assigned in a 1:1:1 ratio to three groups. Treatment group 1 and group 2 received 90 µg and 180 µg of nebulized PegIFNα-2b, respectively, while the control group was administered a combination of 180 µg PegIFNα-2b and 15 mg inhalable Ambroxol Hydrochloride solution, all in a single dose. Safety, tolerability, and blood drug concentration were assessed, along with blood neopterin levels for pharmacokinetic and pharmacodynamic evaluation.</p><p><strong>Results: </strong>The incidence of adverse events (AEs) was 38.9% (7/18) with no significant difference among the groups (P > 0.05). AEs included anemia (N = 5) and leukopenia (N = 2), predominantly of grade 1 severity (6/7), with no severe events. Blood PegIFNα-2b concentrations were below detection limits in most subjects, except one in treatment group 2. Neopterin levels were generally low in treatment group 1 and the control group, with slightly higher observed in most subjects of treatment group 2, but differences were not significant (P > 0.05).</p><p><strong>Conclusions: </strong>Nebulized PegIFNα-2b at doses of 90 µg and 180 µg showed acceptable safety and tolerability. Minimal systemic absorption was observed following inhalation. Further studies are needed to explore its potential, especially in patients with lower respiratory tract infections.</p><p><strong>Clinical trial registration: </strong>ChiCTR2300074909, retrospectively registered in https://www.chictr.org.cn/ at 20 August 2023.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"99"},"PeriodicalIF":2.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970016","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":"Comparative study on drug encapsulation and release kinetics in extracellular vesicles loaded with snake venom L - amino acid oxidase.","authors":"Divya Ramesh, Shankar M Bakkannavar, Vinutha R Bhat, K Sreedhara Ranganath Pai, Krishna Sharan","doi":"10.1186/s40360-025-00938-8","DOIUrl":"10.1186/s40360-025-00938-8","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to evaluate the potential of plasma-derived extracellular vesicles (EVs) as drug delivery carriers by employing two drug-loading techniques: coincubation and freeze-thaw cycles.</p><p><strong>Methods: </strong>EVs isolated via the polyethylene glycol (PEG) precipitation method were characterized via nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). The size of the particles was 200.1 ± 66.6 nm. The isolated vesicles were loaded with 1000 µg/ml snake venom L amino acid oxidase (SVLAAO) via the coincubation method and subjected to freeze-thaw cycles to prepare a novel formulation. The encapsulation efficiency (EE) of the loaded EVs was analysed at 30 and 60 min, and in vitro drug release profiles were evaluated for both methods and kinetic model for the same was determined.</p><p><strong>Results: </strong>The coincubation method achieved an EE of 58.08 ± 0.060% after 60 min, which was greater than that of the freeze-thaw method (55.80 ± 0.060%). Drug release studies demonstrated that 93% of the drug was released in 8.5 h by the coincubation method, whereas the freeze-thaw method resulted in faster release (99% in 6.5 h) due to membrane disruption. The best fit value (R²) was highest for zero order kinetics model.</p><p><strong>Conclusion: </strong>In conclusion, the coincubation method preserves EV membrane integrity, enabling sustained drug release, making it a promising strategy for targeted drug delivery applications. This study highlights plasma-derived EVs as innovative carriers for therapeutic delivery.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"98"},"PeriodicalIF":2.8,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12063349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953746","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":"Effect of CYP3A4 inhibitor and induction on the pharmacokinetics and safety of FHND9041, a novel EGFR T790M inhibitor, in healthy Chinese.","authors":"Chang Lu, Dongmei Cheng, Yunqiu Xie, Minghong Shang, Rongzhen Chen, Yongqiang Zhu, Jian Gong, Huan Zhou","doi":"10.1186/s40360-025-00930-2","DOIUrl":"https://doi.org/10.1186/s40360-025-00930-2","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Non-small cell carcinoma is the main pathologic type of lung cancer, and a large number of clinical trials have shown that epidermal growth factor receptor tyrosinase inhibitors exhibit superior clinical efficacy and lower toxicity compared with chemotherapy. FHND9041 is a new irreversible EGFR T790M mutation-selective small molecule kinase inhibitor, a third-generation EGFR inhibitor developed by Nanjing Chuangte Pharmaceutical Technology Co., Ltd. The aim of this study was to evaluate the effects of oral Itraconazole capsules and oral Rifampicin capsules on the pharmacokinetic profile and safety and tolerability of a single oral dose of FHND9041 capsules in healthy Chinese male subjects.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Patients and methods: &lt;/strong&gt;This study employed a single-center, open-label, fixed-sequence design, comprising two parallel groups: Group 1 received FHND9041 40 mg in combination with Itraconazole, while Group 2 received Rifampicin in combination with FHND9041 80 mg. Each group enrolled 16 subjects for a two-period study, with the first period involving monotherapy and the second period involving co-administration. All subjects participating in this clinical trial were healthy adult Chinese males.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In healthy subjects, after a single oral administration of 40 mg FHND9041 capsules, the corrected geometric mean ratios (90% confidence intervals) of FHND9041 C&lt;sub&gt;max&lt;/sub&gt;, AUC&lt;sub&gt;0 - last&lt;/sub&gt;, and AUC&lt;sub&gt;0 - inf&lt;/sub&gt; when co-administered with itraconazole capsules compared to the monotherapy phase were 111.46% (103.26 - 120.30%), 169.53% (156.21 - 183.99%), and 168.25% (156.26 - 181.15%), respectively. The 90% confidence interval for C&lt;sub&gt;max&lt;/sub&gt; fell within the 80-125% range, while the 90% confidence intervals for both AUC&lt;sub&gt;0 - last&lt;/sub&gt; and AUC&lt;sub&gt;0 - inf&lt;/sub&gt; exceeded the 80-125% range. Following a single oral dose of 80 mg FHND9041 capsules, the adjusted geometric mean ratios (90% confidence intervals) of C&lt;sub&gt;max&lt;/sub&gt;, AUC&lt;sub&gt;0 - last&lt;/sub&gt;, and AUC&lt;sub&gt;0 - inf&lt;/sub&gt; for FHND9041 during co-administration with Rifampicin compared to monotherapy were 52.12% (41.95 - 64.74%), 16.47% (13.34 - 20.31%), and 16.51% (13.56 - 20.09%), respectively. The 90% confidence intervals for C&lt;sub&gt;max&lt;/sub&gt;, AUC&lt;sub&gt;0 - last&lt;/sub&gt;, and AUC&lt;sub&gt;0 - inf&lt;/sub&gt; all fell outside the 80 - 125% range. No serious adverse events occurred during the trial.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Co-administration with Rifampicin significantly reduced the exposure of FHND9041. Therefore, it is recommended to avoid co-administration of FHND9041 with Rifampicin and other potent CYP3A4 inducers. Conversely, co-administration with Itraconazole significantly increased the total exposure of FHND9041. Caution is advised when FHND9041 is co-administered with Itraconazole or other strong CYP3A4 inhibitors. Close monitoring of tolerability during co-administration is essential, and dose reduction may be nec","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"97"},"PeriodicalIF":2.8,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970119","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 drug events observed with intrathecal magnesium sulfate as an adjuvant to bupivacaine for spinal anesthesia in patients undergoing elective cesarean section: a meta-analysis.","authors":"Yuanhui Zhang, Yan Huang, Jun Li","doi":"10.1186/s40360-025-00933-z","DOIUrl":"10.1186/s40360-025-00933-z","url":null,"abstract":"<p><strong>Introduction: </strong>Today, the number of cesarean section has drastically increased. Newer scientific reports have shown Magnesium sulfate (MgSO4) to have favorable outcomes for anesthesia. In this analysis, we aimed to systematically compare the adverse drug events observed with intrathecal MgSO4 as an adjuvant to bupivacaine for spinal anesthesia in patients undergoing elective cesarean section.</p><p><strong>Methods: </strong>MEDLINE, EMBASE, Web of Science, Google scholar, http://www.</p><p><strong>Clinicaltrials: </strong>gov , and the Cochrane database were searched for relevant publications comparing the adverse drug events observed with intrathecal MgSO4 as an adjuvant to bupivacaine for spinal anesthesia in patients undergoing elective cesarean section. The RevMan software version 5.4 was used to analyze data in this analysis. Risk ratios (RR) with 95% confidence intervals (CIs) were used to represent analysis for the dichotomous data whereas weighted mean difference (WMD) with 95% CI was used to represent results using continuous data. Heterogeneity was assessed by the Q statistic and the I2 statistic tests.</p><p><strong>Results: </strong>Eleven studies with a total number of 895 participants were included in this analysis whereby 466 patients were assigned to intrathecal MgSO4 and 429 participants were assigned to a control group. The main results of this analysis show that intrathecal MgSO4 as an adjuvant to bupivacaine was associated with a significantly lower risk of shivering (RR: 0.63, 95% CI: 0.48 - 0.83; P = 0.001). In addition, the risks for hypotension (RR: 1.11, 95% CI: 0.86 - 1.44; P = 0.40), nausea and vomiting (RR: 1.08, 95% CI: 0.76 - 1.54; P = 0.65), pruritus (RR: 0.77, 95% CI: 0.51 - 1.17; P = 0.22), and bradycardia (RR: 4.45, 95% CI: 0.97 - 20.36; P = 0.05) were not significantly increased. The sensory (WMD: 23.15, 95% CI: 7.83 - 38.48; P = 0.003), and motor block duration (WMD: 24.29, 95% CI: 16.36 - 32.23; P = 0.00001) and the duration of spinal anesthesia (WMD: 29.24, 95% CI: 13.61 - 44.87; P = 0.0002) were significantly in favor of MgSO4.</p><p><strong>Conclusion: </strong>Intrathecal MgSO4 as an adjuvant to bupivacaine was associated with a significantly lower risk of shivering without causing any increase in other adverse drug events in patients undergoing elective cesarean section. Efficacy outcomes were also appreciated. Larger studies should be able to confirm this hypothesis.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"96"},"PeriodicalIF":2.8,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12054056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961433","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}