Pharmaceuticals最新文献

{"title":"The Clinical Pharmacokinetics and Pharmacodynamics of Glimepiride-A Systematic Review and Meta-Analysis.","authors":"Mubara Azhar, Mohammed S Alasmari, Ammara Zamir, Hamid Saeed, Faleh Alqahtani, Tanveer Ahmad, Muhammad Fawad Rasool","doi":"10.3390/ph18010122","DOIUrl":"10.3390/ph18010122","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Glimepiride (GLM), a commonly used sulphonylurea drug for the management of type 2 diabetes mellitus (T2DM), has been the subject of numerous studies exploring its kinetic behaviors. However, a comprehensive evaluation that synthesizes all available pharmacokinetic (PK) data across diverse populations remains limited. This systematic review aims to provide detailed knowledge about the pharmacokinetics (PK), the associated pharmacodynamics (PD), and the drug interactions of GLM, which can be used to assess key parameters and identify factors influencing variability across diverse populations and clinical settings. <b>Methods:</b> A systematic search of the peer-reviewed literature was combined using major databases-Google Scholar, PubMed, Cochrane, and ScienceDirect, to identify studies reporting the PK of GLM. Following the data extraction, a meta-analysis using a random effect (RE) model was performed, where feasible, to quantitatively assess the variability of key PK parameters across different studies to create a more robust PK parameter estimate. <b>Results:</b> The final screening has yielded 40 articles. The area under the curve (AUC_0-∞) and the peak concentration (C_max) rise proportionately with increasing doses, depicting the linear kinetics of GLM. The subjects with genotype CYP2C9 *1/*3 depicted a 4-fold higher (AUC_0-∞) as compared to that of the CYP2C9 *1/*1 population. Preliminary meta-analysis results indicated significant variability in (AUC_0-∞) and C_max values among different studies. Heterogeneity across studies was high, warranting the use of RE models. <b>Conclusions:</b> The findings of this review would be helpful in the development and evaluation of PK models that may aid in suggesting individualized dosing.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11768776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041214","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":"2-Aminothiophene Derivatives-New Drug Candidates Against Leishmaniasis: Drug Design, Synthesis, Pharmacomodulation, and Antileishmanial Activity.","authors":"Rodrigo Santos Aquino de Araújo, Vitória Gaspar Bernardo, Robert da Silva Tibúrcio, Danilo Cesar Galindo Bedor, Michel Leandro de Campos, Roberto Pontarolo, Julyanne Maria Saraiva de Sousa, Klinger Antonio da Franca Rodrigues, Marcus Tullius Scotti, Anuraj Nayarisseri, Pascal Marchand, Francisco Jaime Bezerra Mendonça-Junior","doi":"10.3390/ph18010125","DOIUrl":"10.3390/ph18010125","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Leishmaniasis is one of the 20 Neglected Tropical Diseases according to the WHO, affecting approximately 12 million people in four continents, generating serious public health problems. The lack of therapeutic options, associated with toxicity and the emergence of resistance to the few available drugs, makes it urgent to develop new drug options. In this context, the aims of this work are to expand the knowledge about the pharmacophore group responsible for the antileishmanial potential of 2-aminothiophene derivatives. Thus, new compounds were synthesized containing chemical modifications at the C-3, C-4, and C-5 positions of the 2-aminothiophene ring, in addition to the S-Se bioisosterism. <b>Methods</b>: Dozens of 2-AT and 2-aminoselenophen (2-AS) derivatives were sequentially synthesized through applications of the Gewald reaction and were then evaluated in vitro for their activities against <i>L. amazonensis</i> and for cytotoxicity against macrophages. <b>Results</b>: Several series of compounds were synthesized, and it was possible to identify some substitution patterns favorable to the activity generating compounds with IC₅₀ values below 10 µM, such as the non-essentiality of the presence of a carbonitrile group at C-3; the importance of the presence and size of cycloalkyl/piperidinyl chains at C-4 and C-5 in modulating the activity; and the increase in activity without affecting the safety of the S/Se bioisosteric substitution. <b>Conclusions</b>: Taken together, these findings reaffirm the great potential of 2-aminothiophenes to generate antileishmanial drug candidates and offers contributions to the drug design of compounds with an even more promising profile for the problem of leishmaniasis.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11768359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041284","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":"Sustainable Skincare Innovation: Cork Powder Extracts as Active Ingredients for Skin Aging.","authors":"Ana Silva, Cláudia Pinto, Sara Cravo, Sandra Mota, Liliana Rego, Smeera Ratanji, Clara Quintas, Joana Rocha E Silva, Carlos Afonso, Maria Elizabeth Tiritan, Honorina Cidade, Teresa Cruz, Isabel F Almeida","doi":"10.3390/ph18010121","DOIUrl":"10.3390/ph18010121","url":null,"abstract":"<p><p><b>Background</b>: An emerging practice within the concept of circular beauty involves the upcycling of agro-industrial by-products. Cork processing, for instance, yields by-products like cork powder, which presents an opportunity to create value-added cosmetic ingredients. Building upon our previous research, demonstrating the antioxidant potential of hydroalcoholic extracts derived from two distinct cork powders (P0 and P1), in this work, aqueous extracts were prepared and analyzed. The safety and bioactivities of the newly obtained aqueous extracts, as well as the 30% ethanol extracts, previously reported to be the most promising for skin application, were also evaluated. <b>Methods</b>: Aqueous extracts were obtained from cork powders (P0 and P1) and the identification and quantification of some polyphenols was achieved by liquid chromatography (LC). Antioxidant potential was screened by DPPH method and the bioactivity and safety of extracts were further explored using cell-based assays. <b>Results</b>: All extracts exhibited a reduction in age-related markers, including senescence-associated beta-galactosidase (SA-β-gal) activity. Additionally, they demonstrated a pronounced anti-inflammatory effect by suppressing the production of several pro-inflammatory mediators in macrophages upon lipopolysaccharide stimulation. Moreover, the extracts upregulated genes and proteins associated with antioxidant activity, such as heme oxygenase 1. The aqueous extract from P1 powder was especially active in reducing pro-inflammatory mediators, namely the <i>Nos2</i> gene, inducible nitric oxide protein levels, and nitric oxide production. Moreover, it did not induce skin irritation, as assessed by the EpiSkin test, in compliance with the OECD Test Guidelines. <b>Conclusions</b>: Overall, our findings underscore the potential of aqueous extracts derived from cork waste streams to mitigate various hallmarks of skin aging, including senescence and inflammaging, and their suitability for incorporation into cosmetics formulations. These results warrant further exploration for their application in the pharmaceutical and cosmetic industries and could foster a sustainable and circular bioeconomy.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041243","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":"Fully Automated Production of (((<i>S</i>)-1-Carboxy-5-(6-([¹⁸F]fluoro)-2-methoxynicotinamido)pentyl)carbamoyl)-l-glutamic Acid ([¹⁸F]JK-PSMA-7).","authors":"Philipp Krapf, Thomas Wicher, Boris D Zlatopolskiy, Johannes Ermert, Bernd Neumaier","doi":"10.3390/ph18010119","DOIUrl":"10.3390/ph18010119","url":null,"abstract":"<p><p><b>Background:</b> The radiotracer [¹⁸F]JK-PSMA-7, a prostate cancer imaging agent for positron emission tomography (PET), was previously synthesized by indirect radiofluorination using an ¹⁸F-labeled active ester as a prosthetic group, which had to be isolated and purified before it could be linked to the pharmacologically active Lys-urea-Glu motif. Although this procedure could be automated on two-reactor modules like the GE TRACERLab FX2N (FXN) to afford the tracer in modest radiochemical yields (RCY) of 18-25%, it is unsuitable for cassette-based systems with a single reactor. <b>Methods:</b> To simplify implementation on an automated synthesis module, the radiosynthesis of [¹⁸F]JK-PSMA-7 was devised as a one-pot, two-step reaction. The new method is based on direct (\"late-stage\") radiofluorination of an appropriate onium triflate precursor and subsequent deprotection with <i>ortho</i>-phosphoric acid. It was successfully established on the cassette-based Trasis AllInOne (AIO) module. <b>Results:</b> Overall, the new protocol enabled the production of [¹⁸F]JK-PSMA-7 in activity yields of 39 ± 4% (RCY = 58%) with an overall synthesis time of about 1 h. In a single production run with an initial activity of 36-43 GBq, 13-19 GBq of [¹⁸F]JK-PSMA-7 with a radiochemical purity of >99% was obtained. <b>Conclusions:</b> We have established a highly reliable, GMP-compliant process for the automated radiosynthesis of [¹⁸F]JK-PSMA-7 on the Trasis AllinOne (AIO) synthesizer, ensuring consistent and efficient production of this radioligand.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041232","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":"Opioid System and Epithelial-Mesenchymal Transition.","authors":"Marzena Łazarczyk, Dominik Skiba, Michel-Edwar Mickael, Kinga Jaskuła, Agata Nawrocka, Piotr Religa, Mariusz Sacharczuk","doi":"10.3390/ph18010120","DOIUrl":"10.3390/ph18010120","url":null,"abstract":"<p><p>Opioids are a challenging class of drugs due to their dual role. They alleviate pain, but also pose a risk of dependency, or trigger constipation, particularly in cancer patients, who require the more potent painkillers in more advanced stages of the disease, closely linked to pain resulting from general inflammation, bone metastases, and primary or secondary tumour outgrowth-related nerve damage. Clinicians' vigilance considering treatment with opioids is necessary, bearing in mind extensive data accumulated over decades that have reported the contribution of opioids to immunosuppression, tumour progression, or impaired tissue regeneration, either following opioid use during surgical tumour resection and post-surgical pain treatment, or as a result of other diseases like diabetes, where chronic wounds healing constitutes a challenge. During last few years, an increasing trend for seeking relationships between opioids and epithelial-mesenchymal transition (EMT) in cancer research can be observed. Transiently lasting EMT is desirable during wound healing, but in cancer, or vital organ fibrogenesis, EMT appears to be an obstacle to overcome, forcing to adjust treatment strategies that would reduce the risk for worsening of the disease outcome and patient prognosis. The same opioid may demonstrate promoting or inhibitory effect on EMT, dependently on various conditions in particular clinical cases. We have summarized current findings on this issue to uncover some rules that govern opioid-mediated EMT induction or repression; however, many aspects still remain to be elucidated.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11768736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040717","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":"(<i>E</i>)-1-(3-(3-Hydroxy-4-Methoxyphenyl)-1-(3,4,5-Trimethoxyphenyl)allyl)-1<i>H</i>-1,2,4-Triazole and Related Compounds: Their Synthesis and Biological Evaluation as Novel Antimitotic Agents Targeting Breast Cancer.","authors":"Gloria Ana, Azizah M Malebari, Sara Noorani, Darren Fayne, Niamh M O'Boyle, Daniela M Zisterer, Elisangela Flavia Pimentel, Denise Coutinho Endringer, Mary J Meegan","doi":"10.3390/ph18010118","DOIUrl":"10.3390/ph18010118","url":null,"abstract":"<p><p><b>Background/Objectives:</b> The synthesis of (<i>E</i>)-1-(1,3-diphenylallyl)-1<i>H</i>-1,2,4-triazoles and related compounds as anti-mitotic agents with activity in breast cancer was investigated. These compounds were designed as hybrids of the microtubule-targeting chalcones, indanones, and the aromatase inhibitor letrozole. <b>Methods</b>: A panel of 29 compounds was synthesized and examined by a preliminary screening in estrogen receptor (ER) and progesterone receptor (PR)-positive MCF-7 breast cancer cells together with cell cycle analysis and tubulin polymerization inhibition. <b>Results</b>: (<i>E</i>)-5-(3-(1<i>H</i>-1,2,4-triazol-1-yl)-3-(3,4,5-trimethoxyphenyl)prop-1-en-1-yl)-2-methoxyphenol <b>22b</b> was identified as a potent antiproliferative compound with an IC₅₀ value of 0.39 mM in MCF-7 breast cancer cells, 0.77 mM in triple-negative MDA-MB-231 breast cancer cells, and 0.37 mM in leukemia HL-60 cells. In addition, compound <b>22b</b> demonstrated potent activity in the sub-micromolar range against the NCI 60 cancer cell line panel including prostate, melanoma, colon, leukemia, and non-small cell lung cancers. G₂/M phase cell cycle arrest and the induction of apoptosis in MCF-7 cells together with inhibition of tubulin polymerization were demonstrated. Immunofluorescence studies confirmed that compound <b>22b</b> targeted tubulin in MCF-7 cells, while computational docking studies predicted binding conformations for <b>22b</b> in the colchicine binding site of tubulin. Compound <b>22b</b> also selectively inhibited aromatase. <b>Conclusions</b>: Based on the results obtained, these novel compounds are suitable candidates for further investigation as antiproliferative microtubule-targeting agents for breast cancer.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041282","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 Stability-Indicating Ultra High-Performance Liquid Chromatography with Diode Array Detector and Tandem Mass Spectrometry Method Applied for the Forced Degradation Study of Ritlecitinib: An Appraisal of Green and Blue Metrics.","authors":"Jelena Kovačić, Daniela Amidžić Klarić, Nikša Turk, Željko Krznarić, Emma Riordan, Ana Mornar","doi":"10.3390/ph18010124","DOIUrl":"10.3390/ph18010124","url":null,"abstract":"<p><strong>Background/objectives: </strong>Janus kinase inhibitors open new horizons for small-molecule drugs in treating inflammatory bowel disease, with ritlecitinib demonstrating significant efficacy in clinical trials for ulcerative colitis and Crohn's disease. Ritlecitinib, a second-generation JAK3 inhibitor, is a novel therapeutic agent for alopecia areata and other autoimmune conditions.</p><p><strong>Methods: </strong>A new stability-indicating UHPLC-DAD-MS/MS method was developed, validated, and applied for a forced degradation study of ritlecitinib under ICH guidelines.</p><p><strong>Results: </strong>The method demonstrated high specificity, sensitivity (LOD: 0.04 µg/mL; LOQ: 0.14 µg/mL), precision (RSD ≤ 0.15%), and accuracy (99.9-100.3%). Forced degradation studies under acidic, basic, oxidative, thermal, and photolytic conditions revealed four novel degradation products. Basic degradation followed second-order kinetics, while oxidative degradation followed zero-order kinetics.</p><p><strong>Conclusions: </strong>The validated method reliably characterized ritlecitinib's stability and degradation products, providing essential data for optimizing formulation, determining proper storage conditions, anticipating drug-excipient interactions, and ensuring quality control. The eco-friendliness and applicability of the developed forced degradation procedure were evaluated using various green and blue metric tools. Incorporating green analytical principles underscores its potential for sustainable pharmaceutical analysis.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11768339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040290","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":"Investigating the Effect and Potential Mechanism of Rhamnetin 3-<i>O</i>-α-Rhamnoside on Acute Liver Injury In Vivo and In Vitro.","authors":"Dandan Deng, Borong Zhao, Hong Yang, Songsong Wang, Ziying Geng, Jiangtao Zhou, Guane Yang, Liwen Han","doi":"10.3390/ph18010116","DOIUrl":"10.3390/ph18010116","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Rhamnetin 3-<i>O</i>-α-rhamnoside (ARR) is a major flavonoid of the herb <i>Loranthus tanakae</i> Franch. & Sav., which has been used for treating liver diseases in China. However, the protective effect of ARR on the liver has not been reported. <b>Methods</b>: Zebrafish larvae were used as a visual animal model, and liver injury was induced by thioacetamide (TAA) for an acute liver injury (ALI) model. The hepatoprotective activity of ARR was evaluated by assessing liver morphology, liver function indices, oxidative stress, and the mRNA expression levels of inflammation-related genes in the zebrafish model. Additionally, the ROS level, inflammatory factors, and protein expression related to the IKKβ/NF-κB signaling pathway were measured to investigate a potential mechanism of ARR in HepG2 cells. <b>Results</b>: ARR ameliorated TAA-induced growth retardation, reduced liver injury phenotypes, and decreased oxidative stress in the zebrafish. ARR was also able to lower ROS levels in HepG2 cells, effectively inhibit the overactivation of the IKKβ/NF-κB signaling pathway in pathological conditions, inhibit NF-κB p65 translocation from the cytoplasm to the nucleus, and reduce the release of intracellular inflammatory factors. <b>Conclusions</b>: ARR showed significant protective activity against TAA-induced liver injury in in vivo and in vitro models, and its potential mechanism was closely related to the IKKβ/NF-κB signaling pathway.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041264","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":"Quinazolinone Derivative MR2938 Protects DSS-Induced Barrier Dysfunction in Mice Through Regulating Gut Microbiota.","authors":"Ling Lv, Mireguli Maimaitiming, Jichen Yang, Shuli Xia, Xin Li, Pingyuan Wang, Zhiqing Liu, Chang-Yun Wang","doi":"10.3390/ph18010123","DOIUrl":"10.3390/ph18010123","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Ulcerative colitis (UC), a chronic inflammatory bowel disease (IBD), is characterized by colorectal immune infiltration and significant microbiota compositional changes. Gut microbiota homeostasis is necessary to maintain the healthy state of humans. MR2938, a quinazolin-4(3H)-one derivative derived from the marine natural product penipanoid C, alleviated DSS-induced colitis in a dose-dependent manner. Herein, we aimed to investigate the impact of MR2938 on the gut microbiota in dextran sodium sulfate (DSS)-induced colitis in mice and to elucidate the role of the gut microbiota in the therapeutic mechanism of MR2938 for alleviating colitis. <b>Methods</b>: Acute colitis was induced with DSS in mice. Mice were administered with 100 mg/kg or 50 mg/kg of MR2938. Cecal content was also preserved in liquid nitrogen and subsequently analyzed following 16S RNA sequencing. Antibiotic cocktail-induced microbiome depletion was performed to further investigate the relationship between MR2938 and gut microbiota. The inflammatory factor levels were performed by quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). Alcian blue staining and immunofluorescence were used to estimate the intestinal barrier. <b>Results</b>: The 16S rRNA sequencing revealed microbiota modulation by MR2938. Compared with the model group, the 100 mg/kg MR2938 group was associated with higher abundances of <i>Entercoccus</i> and a lower abundance of <i>Staphylococcus</i>, while the 50 mg/kg MR2938 group was associated with higher abundances of <i>Lactobacillus</i> and a lower abundance of <i>Staphylococcus</i>. The antibiotic-mediated microbiota depletion experiments demonstrated that the gut microbiota primarily contributed to barrier function protection, with little impact on inflammatory factor levels during the MR2938 treatment. <b>Conclusions</b>: These findings suggest that intestinal flora play a crucial role in MR2938's therapeutic mechanism for alleviating colitis.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11768254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041126","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":"Ceftazidime-Avibactam Versus Colistin for the Treatment of Multidrug-Resistant <i>Pseudomonas aeruginosa</i> Infections: A Multicenter Cohort Study.","authors":"Thamer A Almangour, Zakiyah Alkherb, Leen Ghonem, Mohammed Al Musawa, Abdullah Almohaizeie, Sara Almuhisen, Aminah Alharbi, Nader Damfu, Doaa Aljefri, Jeelan Alghaith, Awaly Alfozan, Ahlam Alghamdi, Ahmad Aljabri, Abdullah A Alhifany, Mohammed Alessa, Yazed Saleh Alsowaida","doi":"10.3390/ph18010108","DOIUrl":"10.3390/ph18010108","url":null,"abstract":"<p><p><b>Purpose:</b> To evaluate the real-world evidence of ceftazidime-avibactam (CAZ-AVI) compared to intravenous colistin for the treatment of multidrug-resistant (MDR) <i>P. aeruginosa</i> infections. <b>Method:</b> This is a multicenter, retrospective cohort study conducted in the period between 2017 and 2023 at five institutions for patients who received either CAZ-AVI or colistin-based regimens for treating MDR <i>P. aeruginosa</i> infections. Outcomes were compared using multivariate logistic regression analysis. <b>Result:</b> Among the screened patients, 203 patients were included: 89 in the CAZ-AVI group and 114 in the colistin group. A total of 57% presented with pneumonia, 21% with bacteremia, and 61% were in the intensive care unit. The rate of clinical cure was significantly higher among patients who received CAZ-AVI (67% vs. 50%; OR, 2.07; 95% CI, 1.16-3.68). The rate of in-hospital mortality was numerically lower among patients who received CAZ-AVI (40% vs. 49%; OR, 0.58; 95% CI, 0.33-1.03). The rate of AKI was significantly lower among patients who received CAZ-AVI (15% vs. 43%; OR, 0.23; 95% CI, 0.11-0.45). <b>Conclusion:</b> CAZ-AVI was more effective in treating MDR <i>P. aeruginosa</i> infections and showed a better safety profile compared to colistin. Thus, CAZ-AVI could be a better alternative for treating MDR <i>P. aeruginosa</i> infections.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040896","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}