BMC Pharmacology & Toxicology最新文献

{"title":"The efficacy and safety of belzutifan inhibitor in patients with advanced or metastatic clear cell renal cell carcinoma: a meta-analysis.","authors":"Ge Song, Song Xue, Yingming Zhu, Chunling Wu, Xiaowei Ji","doi":"10.1186/s40360-024-00828-5","DOIUrl":"https://doi.org/10.1186/s40360-024-00828-5","url":null,"abstract":"<p><strong>Background: </strong>The belzutifan is a hypoxia inducible factor-2 alpha (HIF-2α) inhibitor for the treatment of advanced or metastatic clear cell renal cell carcinoma (mccRCC) and has exhibited good safety and efficacy in clinical trials. We conducted a meta-analysis of relevant studies to further clarify the efficacy and safety of belzutifan for the treatment of mccRCC.</p><p><strong>Methods: </strong>Multiple databases and abstracts from major scientific meetings were systematically reviewed for eligible articles published before June 1, 2024. The following outcomes were analyzed: objective response rate (ORR), disease control rate (DCR), median duration of response (mDOR), median progression-free survival (mPFS), median overall survival (mOS), and treatment-related adverse events (TRAes). 426 records were reviewed, and data were extracted by at least two individuals.</p><p><strong>Results: </strong>Seven studies involving 715 patients were included in this meta-analysis. The pooled ORR was 34% (95% confidence interval [CI]: 23-46%), the DCR was 79% (95% CI: 66-90%), the mDOR was 21.8 months (95% CI: 14.82-28.78), and the mPFS time was 8.8 months (95% CI: 6.15-11.44). The pooled incidence of grade 3-5 TRAes was 46%, and the most common TRAe was anemia. Further subgroup analysis revealed that, compared with belzutifan monotherapy, the combination of belzutifan with tyrosine kinase inhibitors (TKIs) as second- or later-line therapy was associated with a statistically significant increase in the ORR. Toxicity was also greater with combined inhibition therapy.</p><p><strong>Conclusions: </strong>Our meta-analysis revealed moderate antitumor activity and a manageable safety profile of the inhibitor belzutifan in patients with mccRCC.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"100"},"PeriodicalIF":2.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Data mining in FAERS: association of newer-generation H1-antihistamines with nervous system disorders.","authors":"Weiping Hu, Hailong Li, Linan Zeng, Jing Gan, Chenghong Feng, Li Chen, Lingli Zhang","doi":"10.1186/s40360-024-00822-x","DOIUrl":"https://doi.org/10.1186/s40360-024-00822-x","url":null,"abstract":"<p><strong>Background: </strong>H1-antihistamines are widely used to treat symptoms depending on histamine release in a variety of conditions. However, neurological adverse events have been reported in post-marketing surveillance studies and there are limited literatures comparing the neurological disorders associated with newer-generation H1-antihistamines from real-world datasets.</p><p><strong>Aims: </strong>We performed a comparative analysis of nervous system disorders and several newer-generation H1-antihistamines including: cetirizine, loratadine, levocetirizine, desloratadine and fexofenadine.</p><p><strong>Methods: </strong>Disproportionality analysis was used to identify the suspected drug neurological adverse events associated with H1-antihistamines of interest via the Food and Drug Administration Adverse Event Reporting System. The proportional reporting ratio (PRR), χ² (chi-square) and the reporting odds ratio (ROR) with 95% confidence interval (CI) were used to estimate the association.</p><p><strong>Results: </strong>AE reports of 43,815 cases from 2017 to 2021 were extracted from FAERS. The H1-antihistamines included in our study were associated with various neurological adverse events that could be classified into 12 aspects, containing 42 preferred terms. The majority of adverse event reports were concentrated at somnolence: cetirizine [N = 1342, ROR (95%CI) = 11.8 (11.2-12.5), PRR = 10.8, χ² = 11755.4], levocetirizine [N = 1276, ROR(95%CI) = 28.5 (26.7-30.3), PRR = 22.7, χ² = 26218.4], loratadine[N = 516, ROR(95%CI) = 4.6 (4.2-5.0), PRR = 4.4, χ² = 1378.1], desloratadine [N = 33, ROR(95%CI) = 6.1 (4.3-8.6), PRR = 5.8, χ² = 131.9], fexofenadine [N = 498, ROR(95%CI) = 5.0 (4.6-5.5), PRR = 4.8, χ² = 1519.0].</p><p><strong>Conclusion: </strong>Neurological AEs associated with individual newer generation H1-antihistamines of interest varies a lot, whereas somnolence was the most common AE reports. Fexofenadine was highly associated with headaches. Sedative effects associated with levocetirizine and cetirizine should arouse more concern. Seizures significantly associated with levocetirizine and desloratadine were infrequently reported, further research is needed to avoid possible serious outcomes. Patients taking cetirizine probably have higher risk of dystonia and anticholinergic syndrome.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"95"},"PeriodicalIF":2.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential cardioprotective effect of paroxetine against ventricular remodeling in an animal model of myocardial infarction: a comparative study.","authors":"Asma S Alonazi, Sara Almodawah, Rana Aldigi, Anfal Bin Dayel, Maha Alamin, Ahmad R Almotairi, Maha F El-Tohamy, Hana Alharbi, Rehab Ali, Tahani K Alshammari, Nouf M Alrasheed","doi":"10.1186/s40360-024-00824-9","DOIUrl":"https://doi.org/10.1186/s40360-024-00824-9","url":null,"abstract":"<p><strong>Background: </strong>Post-myocardial infarction (MI) remodeling involves various structural and functional changes, such as inflammation and fibrosis. Upregulation of G protein-coupled receptor kinase 2 (GRK2) is linked to the progression of cardiovascular diseases, including myocardial infarction. The inhibitory effects of paroxetine on GRK2 are recognized, yet its protective effect on post-MI remodeling has not been elucidated. Here, we investigated the cardioprotective effect of paroxetine in an animal model of MI, focusing on post-MI cardiac remodeling and comparing its effect to a β-blocker and an angiotensin receptor antagonist.</p><p><strong>Methods: </strong>Albino Wistar rats were divided into five groups (control; untreated MI; and MI pre-treated with either paroxetine, metoprolol, or irbesartan). MI was induced using isoproterenol (100 mg.kg^-1) on days 16 and 17. Cardioprotective effects were determined by assessing markers of cardiac injury, histopathology, inflammation, oxidative stress, and fibrosis. Statistical analysis performed using a one-way analysis of variance, followed by an appropriate post hoc test, the differences between the groups were considered significant when the (P < 0.05).</p><p><strong>Results: </strong>Paroxetine significantly attenuated cardiac injury biomarkers including serum Tn-I and CK-MB levels. In terms of cardiac remodeling, paroxetine significantly reduced the relative HW/BW index and the plasms FGF23 level. Furthermore, it modulated markers of fibrosis, inflammation, and oxidative stress.</p><p><strong>Conclusion: </strong>The current findings suggest that pre-treatment with paroxetine may exert a beneficial effect that protects against post-MI remodeling, including modulating fibrotic, inflammatory, and angiogenesis-related factors. Therefore, the current findings show the promising role of paroxetine as a cardioprotective that attenuates post-MI remodeling processes.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"99"},"PeriodicalIF":2.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of azathioprine in patients with Cronkhite-Canada syndrome: a case series from Peking Union Medical College Hospital.","authors":"Qiushi Xu, Lixin Jin, Chengzhu Ou, Tianming Xu, Zhuo Yang, Runfeng Zhang, Shuang Liu, Xuemin Yan, Gechong Ruan, Ji Li, Jingnan Li","doi":"10.1186/s40360-024-00825-8","DOIUrl":"https://doi.org/10.1186/s40360-024-00825-8","url":null,"abstract":"<p><strong>Background: </strong>Cronkhite-Canada syndrome (CCS) is a rare non-hereditary chronic inflammatory disease characteristic of gastrointestinal polyps and ectodermal abnormalities. Corticosteroid therapy is the mainstay medication for CCS. Few studies indicated immunosuppressants might be the choices for patients with steroid refractory, steroid dependent or intolerant.</p><p><strong>Aim: </strong>To examine the efficacy and safety of azathioprine (AZA) in CCS patients.</p><p><strong>Method: </strong>We retrospectively reviewed the records of 12 CCS patients treated with azathioprine between July 2014 and October 2023 and the clinical data including demographic characteristics, treatment regimen and adverse events were subsequently collected and analyzed. The genetic variants of TPMT and NUDT15 genes were also retrospectively assessed using sanger sequencing in 11 patients.</p><p><strong>Outcome: </strong>All patients were in active stage at baseline and 9 patients (75%) were in combination with corticosteroid. On account of the indication, 6 patients were steroid dependent or intolerant and another 6 patients needed augmentation therapy. The target dose of AZA was 1.0 to 1.5 mg/kg per day. Ten (83.3%) patients achieved clinical response, of whom 3 cases had endoscopic remission and 5 cases had endoscopic improvement respectively. Three (25%) patients suffered from pneumocystis carinii pneumonia, liver dysfunction and leukopenia, respectively, resulting in cessation of AZA in the initial 3 months. Four heterozygous missense variants of TPMT and NUDT15 were identified in four patients. One patient who had TPMT*6 and took AZA with the dose of 2.04 mg/kg per day suffered from severe leukopenia.</p><p><strong>Conclusion: </strong>Azathioprine might be a good alternative medication in CCS patients who are steroid dependent or intolerant, or need augmentation therapy. The adverse events should be closely monitored especially myelosuppression and the tests of TPMT and NUDT15 genotypes before therapy may be helpful for medication guidance.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"96"},"PeriodicalIF":2.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A real-world disproportionality analysis of the US Food and Drug Administration (FDA) adverse event reporting system (FAERS) events for Durvalumab.","authors":"Ting Zou, Zhuoyang Li, Tianhong Wang, Shuang Deng, Siman Wang, Yusi Hua","doi":"10.1186/s40360-024-00821-y","DOIUrl":"https://doi.org/10.1186/s40360-024-00821-y","url":null,"abstract":"<p><strong>Background: </strong>In the past few years, an increasing number of research studies have documented the utilization of durvalumab in the field of immunotherapy for cancerous tumors. However, there remains insufficient documentation regarding its associated adverse event (AEs). In order to enhance our comprehension of its toxicological profile, this investigation retrospectively examined the AEs linked to durvalumab using data from the US Food and Drug Administration adverse event reporting system (FAERS).</p><p><strong>Methods: </strong>Using data from FAERS for the period 2004 to 2024, the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN) and mu-item gamma Poisson shrinker (MGPS) four algorithms were used to quantify durvalumab related AEs. SAS 9.4 was used for statistical analysis.</p><p><strong>Results: </strong>We collected nonduplicated reported 17,629,340 patients from the FAERS database and 19,709 AEs cases in the target population with durvalumab as the primary drug of suspicion. There were 6 significantly disproportionate preferred terms (PTs) that fit all four algorithms simultaneously. The AEs commonly reported include death, radiation pneumonitis, pneumonitis, and lung disorders. Furthermore, durvalumab has been associated with additional AEs, such as metastases to the central nervous system and drug-induced liver injury.</p><p><strong>Conclusions: </strong>The study revealed that durvalumab immunotherapy is associated with AEs including death, radiation pneumonitis, pneumonitis, metastases to the central nervous system, lung disorder and drug-induced liver injury. In clinical practice, it is crucial to be vigilant and prevent the occurrence of these AEs.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"97"},"PeriodicalIF":2.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eco-friendly green synthesis of silver nanoparticles from guajava leaves extract for controlling organophosphorus pesticides hazards, characterization, and in-vivo toxicity assessment.","authors":"Emad Ali Albadawi, Eid Nassar Ali Musa, Hadel Mahroos Ghaban, Neven A Ebrahim, Muayad Saud Albadrani, Ahmed I El-Tokhy","doi":"10.1186/s40360-024-00826-7","DOIUrl":"https://doi.org/10.1186/s40360-024-00826-7","url":null,"abstract":"<p><p>This study explores an eco-friendly approach to mitigate risks associated with organophosphorus insecticides, particularly Chlorpyrifos, by synthesizing silver nanoparticles (AgNPs) using Psidium guajava leaf extract and preparing a nanocomposite (AgNPs/S18) with Chlorpyrifos pesticide. The green-synthesized AgNPs and AgNPs/S18 nanocomposite were characterized using various analytical techniques, confirming the successful synthesis of AgNPs with an average size of 37 nm and forming a stable nanocomposite. Antibacterial assays demonstrated significant activity against Staphylococcus aureus, with AgNPs showing an 87.8% reduction and the nanocomposite achieving a 72% reduction in bacterial population. Cytotoxicity evaluations on normal liver and liver cancer cell lines revealed enhanced cytotoxicity of the nanocomposite compared to AgNPs alone, suggesting potential applications in targeted therapies. In vivo studies on rats revealed the protective effects of AgNPs and the nanocomposite against Chlorpyrifos-induced toxicity in liver and kidney tissues. Histopathological and ultrastructural analyses showed both treatments, particularly the nanocomposite, significantly mitigated cellular damage caused by Chlorpyrifos exposure. These findings suggest that green-synthesized AgNPs and their nanocomposite with Chlorpyrifos offer a promising approach to reducing pesticide hazards while maintaining efficacy. This research contributes to developing safer alternatives in pest management, addressing the need for more environmentally friendly agricultural practices while protecting human health and ecosystems.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"98"},"PeriodicalIF":2.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of vildagliptin versus metformin on hepatic steatosis in type 2 diabetic patients: a randomized controlled trial.","authors":"Asmaa S Mohamed, Hosam M Ahmad, Mohammed A Sharawy, Fatma M M Kamel","doi":"10.1186/s40360-024-00818-7","DOIUrl":"10.1186/s40360-024-00818-7","url":null,"abstract":"<p><strong>Background: </strong>The risk of hepatic steatosis (HS) is elevated in patients with type 2 diabetes mellitus (T2D). Antidiabetic medications may contribute to the prevention or treatment of HS. This study aimed to compare the effects of vildagliptin and metformin on hepatic steatosis in newly diagnosed T2D patients, using the Hepatic Steatosis Index (HSI) and ultrasound grading.</p><p><strong>Methods: </strong>The study included 246 newly diagnosed T2D patients who were randomly assigned to two groups. The first group (117 patients) received 50 mg of vildagliptin orally twice daily. The second group (129 patients) received 500 mg of metformin orally twice daily with meals, and the dosage could be gradually increased by 500 mg per week, up to a maximum daily dose of 2000 mg. Baseline and 6-month follow-up assessments included fasting blood glucose (FBG), HbA1c, weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), the Hepatic Steatosis Index (HSI), and hepatic steatosis grading via ultrasound.</p><p><strong>Results: </strong>Both groups showed significant improvements in FBG, HbA1c, weight, BMI, WC, HC, HSI, and ultrasound grading of hepatic steatosis from baseline to the 6-month follow-up (p < 0.001). The metformin group demonstrated significantly greater reductions in weight and BMI compared to the vildagliptin group (p = 0.001 and p = 0.009, respectively). However, there was no significant difference between the two groups in terms of hepatic steatosis improvement on ultrasound. Correlation analysis revealed that HSI was significantly associated with HbA1c, BMI, WC, and HC (p < 0.001 for all), as well as FBG (p = 0.008), but not with age. The lipid profile, particularly total cholesterol and LDL, was identified as a stronger predictor of hepatic steatosis, based on high AUC, sensitivity, and specificity values.</p><p><strong>Conclusion: </strong>Both vildagliptin and metformin are effective in improving glycemic control in newly diagnosed T2D patients, as evidenced by reductions in FBG and HbA1c levels. Additionally, both drugs significantly reduced the HSI, body weight, and BMI, with metformin showing a more pronounced effect on weight and BMI. Both vildagliptin and metformin effectively decreased hepatic steatosis in T2D patients. Total cholesterol and LDL are important predictors of hepatic steatosis.</p><p><strong>Trial registration: </strong>Trial Registration ID: UMIN000055121, registered on 30/07/2024 (retrospectively registered).</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"94"},"PeriodicalIF":2.8,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11645785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821788","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 comparison of the effects of ticagrelor and clopidogrel in patients with acute ST-segment elevation myocardial infarction: a systematic review and meta-analysis of randomized clinical trials.","authors":"Mehdi Geravandi, Mohammad Nourabi, Sepehr Navabifar, Moein Geravandi, Zahra Hooshanginezhad, Sara Zand, Parinaz Taheri","doi":"10.1186/s40360-024-00817-8","DOIUrl":"10.1186/s40360-024-00817-8","url":null,"abstract":"<p><strong>Background: </strong>Rupture of unstable coronary atherosclerotic plaque leads to acute ST-segment elevation myocardial infarction (STEMI). Dual anti-platelet therapy is one of the main treatments, and the combination of Aspirin and Clopidogrel is recognized as the standard oral regimen in most cases. Ticagrelor is a new generation of P2Y12 receptor inhibitors. We aimed to compare the effect of Ticagrelor and Clopidogrel in the treatment of patients post-STEMI.</p><p><strong>Methods: </strong>This study investigated Pub Med, Scopus, Google Scholar Web of Science, and Embase Cochrane Library clinical trials.gov databases. Heterogeneity between studies was assessed using the I2 index and the Q statistic. The random effects model was used to combine studies and the Funnel plot and Egger's test were used to assess the publication bias.</p><p><strong>Results: </strong>Eleven studies were included in this meta-analysis. 5274 patients in the Ticagrelor and 5,295 patients in the Clopidogrel groups were examined. The mean age of the patients was 58.84 years (2.70) and 59.92 years (3.19) in the Ticagrelor and Clopidogrel groups, respectively. Based on the results of the meta-analysis, compared to Clopidogrel, Ticagrelor had decreased the outcomes of mortality, recurrent myocardial infarction, stroke, and Major Adverse Cardiovascular Events (MACE). However, the post-myocardial infarction bleeding according to Bleeding Academic Research Consortium (BARC) criteria and reperfusion state regarding thrombolysis in myocardial infarction (TIMI) Flow Grading system showed no differences in both groups. However, these effects were not statistically significant.</p><p><strong>Conclusions: </strong>Ticagrelor decreased the chance of mortality, re-infarction, stroke, and MACE in post-STEMI patients compared to clopidogrel. But there was no difference in the chance of major bleedings (BARC ≥ 3) and improvement in TIMI grade flow between these two drugs. However, none of these findings were statistically significant, and more studies are needed to reach definitive results.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"93"},"PeriodicalIF":2.8,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799368","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":"Toxicology study of a tissue anchoring paclitaxel prodrug.","authors":"Rukesh Chinthapatla, Jazz Q Stephens, Isabel B Neumann-Rivera, Nichol M Henderson, Minhua Nie, Hannah R Haynes, Joshua G Pierce, Danielle M Meritet, Yevgeny Brudno, Annie Oh","doi":"10.1186/s40360-024-00819-6","DOIUrl":"10.1186/s40360-024-00819-6","url":null,"abstract":"<p><strong>Background: </strong>Local drug presentation made possible by drug-eluting depots provides benefits for a vast array of diseases, including cancer, microbial infection, and wound healing. Drug-eluting depots provide sustained drug release of therapeutics directly at disease sites with tunable kinetics, remove the need for drugs to access disease sites from circulation, and reduce the side effects associated with systemic therapy. Recently, we introduced an entirely novel approach to local drug presentation named Tissue-Reactive Anchoring Pharmaceuticals (TRAPs). TRAPs enables local drug presentation without any material carriers, capitalizing on innate tissue structures to anchor drugs at the site of administration.</p><p><strong>Methods: </strong>In this report, we comprehensively evaluate the local and systemic toxicological profile of a paclitaxel version of TRAPs in mice by clinical observations, body weight monitoring, histopathological evaluations of injection sites and major organs, as well as blood and urine analyses.</p><p><strong>Results: </strong>We find that intradermal administration of TRAP-paclitaxel does not induce substantial toxic effects. Localized inflammatory responses were observed at the injection sites and secondary minimal, non-specific inflammation was observed in the liver. All other organs displayed unremarkable histological findings.</p><p><strong>Conclusions: </strong>These findings support the potential of TRAP-paclitaxel as a promising candidate for localized cancer treatment, offering high-concentration drug delivery while mitigating scarring and adverse side effects.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"92"},"PeriodicalIF":2.8,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783845","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":"Comparison of the prophylactic effect of cefazolin injection versus oral levofloxacin as prophylactic antibiotic in TURP surgery: a randomized clinical trial.","authors":"Ramin Haghighi, Ahmad Kameli, Abdolah Razi, Dorsa Abroon, Amir Amani","doi":"10.1186/s40360-024-00814-x","DOIUrl":"10.1186/s40360-024-00814-x","url":null,"abstract":"<p><strong>Introduction: </strong>Use of antibiotic prophylaxis before transurethral resection of the prostate (TURP) is highly recommended. However, there is no agreement on the use of a single antibiotic for this purpose. This study aimed to compare the prophylactic effect of cefazolin injection with oral levofloxacin on postoperative complications in TURP surgery.</p><p><strong>Trial design: </strong>Body temperature and urine culture results were obtained two and five days after surgery. Drugs' side effects as well as surgery and catheterization time were also recorded.</p><p><strong>Methods: </strong>In an analytical-comparative trial, the participants were randomly divided into two groups to receive cefazolin or levofloxacin before the surgery.</p><p><strong>Results: </strong>The duration of surgery (min) and catheterization (days) were 41.5 ± 11.7 and 4.7 ± 1.8 for levofloxacin-treated group and 43.9 ± 11.9 and 4.7 ± 1.8 for cefazolin-treated group, respectively. The number of positive urine cultures, 2 and 5 days post-surgery were 12 and 14 for levofloxacin-treated group and 9 and 12 for cefazolin-treated group, respectively. Furthermore, both groups reported one fever two days after surgery and had no fever after 5 days. In total, no significant difference was observed between the two groups. Additionally, no correlation was observed between the demographic data (i.e. age, BMI and prostate volume) and the postoperative complications (i.e. fever and urinary culture tests), except between age and urinary culture 2 days after the surgery.</p><p><strong>Conclusion: </strong>Considering the lack of significant differences between the two groups, the use of oral levofloxacin is suggested as an easy to take and cost-effective alternative to injection of cefazolin before TURP surgery.</p><p><strong>Trial registration: </strong>Iranian registry of clinical trials, IRCT registration number IRCT20160514027893N4, available through www.irct.ir , Registration date: 2024-03-13 (Retrospectively registered).</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"91"},"PeriodicalIF":2.8,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11610085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765881","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}