Pharmaceutical Science Advances最新文献

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Antimicrobial potentials and challenges of paracetamol: A comprehensive reassessment based on database reports 扑热息痛的抗菌潜力和挑战:基于数据库报告的综合再评估
Pharmaceutical Science Advances Pub Date : 2025-12-01 Epub Date: 2025-04-09 DOI: 10.1016/j.pscia.2025.100070
Muhammad Torequl Islam , Raihan Chowdhury , Md. Shimul Bhuia , Md. Sakib Al Hasan , Md. Showkot Akbor , Fardin Farhad , Carolina Bandeira Domiciano , Davi Antas e Silva , Henrique D.M. Coutinho
{"title":"Antimicrobial potentials and challenges of paracetamol: A comprehensive reassessment based on database reports","authors":"Muhammad Torequl Islam ,&nbsp;Raihan Chowdhury ,&nbsp;Md. Shimul Bhuia ,&nbsp;Md. Sakib Al Hasan ,&nbsp;Md. Showkot Akbor ,&nbsp;Fardin Farhad ,&nbsp;Carolina Bandeira Domiciano ,&nbsp;Davi Antas e Silva ,&nbsp;Henrique D.M. Coutinho","doi":"10.1016/j.pscia.2025.100070","DOIUrl":"10.1016/j.pscia.2025.100070","url":null,"abstract":"<div><div>Paracetamol (PMCL) is an analgesic-antipyretic drug. It is frequently used as an over-the-counter (OTC) drug in many countries around the world, especially for headaches, mild pain, and fever. Knowing its toxic effects on the nervous and hepatic systems, it has been combined with the psychoactive drug caffeine. However, PMCL's antipyretic action during fevers caused by various pathogens might be due to its antimicrobial power. Therefore, we have a question about whether PMCL can be used as an OTC medication or not. This review aimed to summarize the antimicrobial activity, facts behind it, possible action mechanisms, and causes of resistance growth, along with the antimicrobial and toxicological impacts of its metabolites, derived products, and combination products, on the basis of database reports. Numerous pieces of evidence suggest that both PMCL and caffeine have broad-spectrum antimicrobial effects. PMCL is evidently effective against gram-positive and gram-negative bacteria, fungi, viruses, and protozoa. Its major toxic metabolite, <em>N</em>-acetyl-p-benzoquinone imine (NAPQI), also has antimicrobial potential. Despite its antimicrobial effects, PMCL has contributed to antimicrobial resistance. In conclusion, according to the findings from database reports, PMCL is not only an analgesic-antipyretic drug, but it also has broad-spectrum antimicrobial potential against many pathogenic gram-positive and gram-negative bacteria and fungi as well as some viruses and protozoa. The use of PMCL as an OTC medication might bring a dangerous health issue in the future among the population, for example, growing microbial resistance and harmful toxicological impacts in different organs in humans.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100070"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Study on the CHJ01 antitumor activity and mechanism via targeting sphingosine kinase 1 in A549 cells CHJ01靶向鞘氨醇激酶1在A549细胞中的抗肿瘤活性及机制研究
Pharmaceutical Science Advances Pub Date : 2025-12-01 Epub Date: 2025-05-26 DOI: 10.1016/j.pscia.2025.100077
Caiyu Liu , Shengmei Gao , Bo Liu , Feipeng Zhang , Yanling Mu , Fuwen Wang , Yan Li
{"title":"Study on the CHJ01 antitumor activity and mechanism via targeting sphingosine kinase 1 in A549 cells","authors":"Caiyu Liu ,&nbsp;Shengmei Gao ,&nbsp;Bo Liu ,&nbsp;Feipeng Zhang ,&nbsp;Yanling Mu ,&nbsp;Fuwen Wang ,&nbsp;Yan Li","doi":"10.1016/j.pscia.2025.100077","DOIUrl":"10.1016/j.pscia.2025.100077","url":null,"abstract":"<div><div>The SphK1 inhibitor development is of great importance for the treatment of non-small cell lung cancer (NSCLC). In this study, CHJ01 which has been previously shown anti-tumor effects was introduced to investigate the detailed antitumor mechanism both <em>in</em> <em>vitro</em> and <em>in vivo</em>. CHJ01 inhibited the A549 ​cell proliferation, migration, and invasion significantly and showed cytotoxicity to A549. CHJ01 induced G0/G1 cell cycle arrest by increasing ceramide levels and altered the expression of TRAF2, Bcl-2, Bax and RELA. CHJ01 inhibited the TRAF2/NF-κB signaling pathway and promoted apoptosis by downregulating Bcl-2 and upregulating Bax. <em>In vivo</em> anti-tumor effects were investigated using a nude mouse ectopic tumor model. CHJ01 reduced the volumes and weights of xenograft tumor in nude mice. CHJ01 induced apoptosis by HE staining and immunohistochemistry assay. These results indicated that CHJ01 can be a potential candidate for the treatment of NSCLC.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100077"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144470078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
GLDC interacts with VPS34 to inhibit tumorigenesis and epithelial-mesenchymal transition in hepatocellular carcinoma GLDC与VPS34相互作用抑制肝癌的肿瘤发生和上皮-间质转化
Pharmaceutical Science Advances Pub Date : 2025-12-01 Epub Date: 2025-04-25 DOI: 10.1016/j.pscia.2025.100072
Zan Song , Hao Dong , Kailing Zhang , Bingke Qiao , Leilei Li , Zhicheng Zhang , Zhili Fan , Jing Li , Yu Li , Mengfei Liu , Ying Liu , Xinyu Gu , Tao Zhang
{"title":"GLDC interacts with VPS34 to inhibit tumorigenesis and epithelial-mesenchymal transition in hepatocellular carcinoma","authors":"Zan Song ,&nbsp;Hao Dong ,&nbsp;Kailing Zhang ,&nbsp;Bingke Qiao ,&nbsp;Leilei Li ,&nbsp;Zhicheng Zhang ,&nbsp;Zhili Fan ,&nbsp;Jing Li ,&nbsp;Yu Li ,&nbsp;Mengfei Liu ,&nbsp;Ying Liu ,&nbsp;Xinyu Gu ,&nbsp;Tao Zhang","doi":"10.1016/j.pscia.2025.100072","DOIUrl":"10.1016/j.pscia.2025.100072","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancer with high mortality and limited therapeutic strategy. Glycine decarboxylase (GLDC) is the key limiting enzyme in glycine breakdown metabolism and acts as oncogene or tumor suppressor to impact tumor onset and progression in a context dependent manner. However, the underlying mechanism of GLDC on autophagy and progression is largely unexplored in HCC. Here, we showed that GLDC overexpression inhibited cell proliferation, cell migration and promoted cell senescence and autophagy in HCC. Intriguingly, induced GLDC remarkably attenuated epithelial-mesenchymal transition (EMT) progress and tumor growth <em>in vitro</em> and <em>in vivo</em>. Mechanically, we demonstrated that GLDC upregulated VPS34 protein and enhanced its interaction with VPS34, thus promoting the association of VPS34 with Beclin1/ATG14 complex and autophagy induction in HCC. Importantly, GLDC acetylation at K514 promoted interaction of GLDC-VPS34, whereas GLDC acetylation-dead mutant K514R abolished their binding. Furthermore, GLDC protein was decreased in HCC tissues compared with para-tumor tissues and reduced GLDC was significantly correlated with poor prognosis of patients. In conclusion, we unveil the key regulatory role of GLDC in autophagy and HCC progression through VPS34 and provide a potential strategy for HCC therapy.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100072"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143927771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enhancing ferroptosis and inhibiting ABCB1 make the novel aldose reductase inhibitor 5F-E a promising sensitizer in liver cancer 增强铁凋亡和抑制ABCB1使新型醛糖还原酶抑制剂5F-E成为一种有前途的肝癌增敏剂
Pharmaceutical Science Advances Pub Date : 2025-12-01 Epub Date: 2025-08-08 DOI: 10.1016/j.pscia.2025.100088
Ziyou Zheng , Zhenqiang Chen , Chao Zhang , Shuling Peng , Jianling Hu , Chanxi Wang , Lujie Liu , Mao-xun Yang , Heru Chen
{"title":"Enhancing ferroptosis and inhibiting ABCB1 make the novel aldose reductase inhibitor 5F-E a promising sensitizer in liver cancer","authors":"Ziyou Zheng ,&nbsp;Zhenqiang Chen ,&nbsp;Chao Zhang ,&nbsp;Shuling Peng ,&nbsp;Jianling Hu ,&nbsp;Chanxi Wang ,&nbsp;Lujie Liu ,&nbsp;Mao-xun Yang ,&nbsp;Heru Chen","doi":"10.1016/j.pscia.2025.100088","DOIUrl":"10.1016/j.pscia.2025.100088","url":null,"abstract":"<div><div>Multidrug resistance (MDR) poses a critical barrier to chemotherapy efficacy. While the promising agents, aldose reductase inhibitors (ARIs), to overcome multidrug resistance (MDR) has been investigated over recent decades, their underlying mechanisms remain unclear and clinically viable candidates are still lacking. In our study, we identified a novel ARI, 5F-E, which exhibited a more potent sensitizing effect on doxorubicin (DOX) resistant HepG2 cells (HepG2/ADR) compared to epalrestat (EPA). Both <strong>5F-E</strong> and EPA were observed to decrease intracellular GSH levels while elevating reactive oxygen species (ROS), Fe<sup>2+</sup> and lipid peroxidation; these effects could be reversed by <em>N</em>-acetyl cysteine (NAC), suggesting that enhanced ferroptosis may be involved in restoring DOX sensitivity. Furthermore, inhibition of AKR1B1 by either compound led to marked reductions in <em>p</em>-STAT3 and SLC7A11 expression, an outcome that was recapitulated by AKR1B1 gene knockdown. The results demonstrate that ARIs exert antitumor effects on HepG2/ADR cells by triggering ferroptosis, a process dependent on AKR1B1/STAT3/SLC7A11 signaling. And, 5F-E, but not EPA, was found to increase intracellular DOX accumulation by inhibiting ABCB1. Our integrated experimental approach reveals that 5F-E exhibits strong chemosensitizing effects against multidrug-resistant liver cancer, highlighting its therapeutic promise.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100088"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Protective effects and metabolomics analysis of dihydromyricetin on cyclophosphamide-induced hepatotoxicity in mice 二氢杨梅素对环磷酰胺所致小鼠肝毒性的保护作用及代谢组学分析
Pharmaceutical Science Advances Pub Date : 2025-12-01 Epub Date: 2025-01-15 DOI: 10.1016/j.pscia.2025.100063
Fei Teng, Haina Wang
{"title":"Protective effects and metabolomics analysis of dihydromyricetin on cyclophosphamide-induced hepatotoxicity in mice","authors":"Fei Teng,&nbsp;Haina Wang","doi":"10.1016/j.pscia.2025.100063","DOIUrl":"10.1016/j.pscia.2025.100063","url":null,"abstract":"<div><div>Cyclophosphamide (CTX) is a chemotherapeutic agent with cytotoxic and immunosuppressive activity. It is used to treat a wide variety of cancers and autoimmune diseases. However, side effects caused by its toxic metabolites, especially hepatotoxicity, limit its clinical application. The natural dihydroflavonol compound dihydromyricetin (DHM) has anticancer, anti-inflammatory, and antioxidant properties. This study aimed to evaluate the protective effects of DHM against CTX-induced hepatotoxicity in mice. Male ICR mice were pretreated with DHM (100, 200, and 400 ​mg/kg b.w.) orally before intraperitoneal injection with CTX (100 ​mg/kg b.w.) for 7 days. The mice were then sacrificed to analyze biochemical and histological parameters as well as metabolomics profiles. DHM ameliorated CTX-induced elevations in the liver index, alanine aminotransferase, aspartate transaminase, and malondialdehyde levels, and pathological changes and increased levels of glutathione and antioxidant enzymes, such as superoxide dismutase and catalase. Based on a KEGG pathway analysis of altered serum and liver metabolites, OXPHOS may play an important role in the observed protective effects. Further analysis revealed that DHM increased the activity of Na<sup>+</sup>-K<sup>+</sup>-ATPase in mice, which affected CTX-induced mitochondrial energy metabolism. To conclude, DHM protected against CTX-induced hepatotoxicity, possibly through reducing oxidative stress and regulating energy metabolism, providing a potential strategy for treatment and prevention.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100063"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeted RNA base editing for therapeutic: mechanisms and advances 靶向RNA碱基编辑用于治疗:机制和进展
Pharmaceutical Science Advances Pub Date : 2025-12-01 Epub Date: 2025-08-18 DOI: 10.1016/j.pscia.2025.100089
Weikai Yan, Xiaocheng Weng
{"title":"Targeted RNA base editing for therapeutic: mechanisms and advances","authors":"Weikai Yan,&nbsp;Xiaocheng Weng","doi":"10.1016/j.pscia.2025.100089","DOIUrl":"10.1016/j.pscia.2025.100089","url":null,"abstract":"<div><div>RNA base editing, which enables RNA base modification through effector proteins guided by targeting systems, is a powerful technology to correct disease-associated point mutations. Although overshadowed by CRISPR-based genome editing, RNA editing has seen rapid development in recent years, with significant improvements in efficiency and precision. In this review, we summarize the core components of RNA base editing systems (RNA-targeting systems and effector proteins) and describe major RNA editing types, including A-to-I, C-to-U, A-to-m<sup>6</sup>A/m<sup>6</sup>A-to-A, and U-to-Ψ base editors, along with their research progress. In addition, we systematically summarize the delivery methods of the developed RNA editors and their initial exploration in treating diseases caused by nonsense mutations. Finally, combining the current development status of the RNA editing related field, we reflect on the problems encountered in the current development of the RNA editing field and offer our own insights on the future development direction.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100089"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144903972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Artificial neural network guided optimization of tenofovir and Cyanovirin-N multipurpose preventive hydrogel formulation developed using the Box Behnken design model 采用Box Behnken设计模型,人工神经网络指导下对替诺福韦和Cyanovirin-N多用途预防水凝胶配方进行优化
Pharmaceutical Science Advances Pub Date : 2025-12-01 Epub Date: 2025-06-21 DOI: 10.1016/j.pscia.2025.100079
Karamot O. Oyediran , Ibilola M. Cardoso-Daodu , Peace Ofonabasi Bassey , Deborah A. Ogundemuren , Ridwan Muhammed , Olusola E. Ojo , Andrew N. Amenaghawon , Chukwuemeka P. Azubuike , Rachna Agarwal , Kondoru Haritha , Margaret O. Ilomunaya
{"title":"Artificial neural network guided optimization of tenofovir and Cyanovirin-N multipurpose preventive hydrogel formulation developed using the Box Behnken design model","authors":"Karamot O. Oyediran ,&nbsp;Ibilola M. Cardoso-Daodu ,&nbsp;Peace Ofonabasi Bassey ,&nbsp;Deborah A. Ogundemuren ,&nbsp;Ridwan Muhammed ,&nbsp;Olusola E. Ojo ,&nbsp;Andrew N. Amenaghawon ,&nbsp;Chukwuemeka P. Azubuike ,&nbsp;Rachna Agarwal ,&nbsp;Kondoru Haritha ,&nbsp;Margaret O. Ilomunaya","doi":"10.1016/j.pscia.2025.100079","DOIUrl":"10.1016/j.pscia.2025.100079","url":null,"abstract":"<div><div>Tenofovir (TNF) is an antiretroviral drug that has being used as a topical microbicide to prevent human immunodeficiency virus transmission (HIV). Cyanovirin-N (CV-N) is a lectin protein that can bind to the HIV envelope glycoprotein and inhibit viral entry. The combination of TNF and CV-N may have synergistic effects and enhance the efficacy of microbicide. The aim of this study was to develop and optimize composite hydrogel formulations containing 1%TNF and 0.0005% CV-N using Box Behnken Design. A three-factor, three-level Box-Behnken design was employed to investigate the effects of the concentrations of PEG<sub>2000</sub>, sodium carboxyl methylcellulose (NaCMC), and calcium chloride on the release of Tenofovir, flux, and mucoadhesion. The mucoadhesion was evaluated by measuring the percent mucin adsorption while flux and release kinetics were evaluated using the Franz cell diffusion method. The optimal hydrogel formulation was found to contain 4% NaCMC, 2% PEG2000 and 1% CaCl<sub>2</sub>. The hydrogel had a pH of 4.5 ​± ​0.017, a viscosity of 275600 ​± ​0.65 ​cP, flux 9806 μg/cm<sup>2</sup>/h for TNF with a drug release of 119, 205.6 μg/cm<sup>2</sup>. The TNF gel exhibited a pseudoplastic rheological behavior with 96.3% muco-adhesion. The study successfully developed an optimized TNF/CV-N mucoadhesive hydrogel, highlighting its potential as an on-demand multipurpose prevention technology (MPT) for HIV. The formulation was optimized to ensure good drug release, flux and mucoadhesion. The optimized hydrogel offers a convenient, effective method for preventing sexually transmitted infections (STIs), addressing critical challenges in drug delivery and user adherence while advancing public health strategies for STIs.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100079"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144517796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Curcumin-loaded gelatin ethosomal gel: A novel approach for anti-inflammatory efficacy 姜黄素明胶溶体凝胶:一种抗炎功效的新方法
Pharmaceutical Science Advances Pub Date : 2025-12-01 Epub Date: 2025-11-04 DOI: 10.1016/j.pscia.2025.100098
Varsha Rawat , Smriti Dewangan , Khomendra Kumar Sarwa , Moonmun Dhara , Shakti Ketan Prusty
{"title":"Curcumin-loaded gelatin ethosomal gel: A novel approach for anti-inflammatory efficacy","authors":"Varsha Rawat ,&nbsp;Smriti Dewangan ,&nbsp;Khomendra Kumar Sarwa ,&nbsp;Moonmun Dhara ,&nbsp;Shakti Ketan Prusty","doi":"10.1016/j.pscia.2025.100098","DOIUrl":"10.1016/j.pscia.2025.100098","url":null,"abstract":"<div><div>The research focuses on enhancing the delivery of curcumin's potent anti-inflammatory properties through a novel approach using a curcumin-loaded gelatine ethosomal gel. Curcumin, known for its therapeutic potential, faces challenges due to poor solubility and bioavailability. The method involved dissolving curcumin, phospholipids, and gelatin to form ethosomes within the gelatin matrix using sonication. Various parameters were evaluated including vesicle size, morphology, entrapment efficiency, drug permeation, stability, and anti-inflammatory activity. The optimized curcumin gelatine ethosomes effectively encapsulated the drug, achieving an entrapment efficiency of 89.52% ​± ​0.1% and substantial drug loading capacity ranging from 75.75% ​± ​0.3% to 85.64% ​± ​0.1%. The formulation exhibited stability with a small vesicle size of 122.08 ​nm, a zeta potential of −36.2 ​mV indicating good stability, and spherical ethosome morphology. TEM images confirmed uniform drug distribution within the ethosome without precipitation or unwanted aggregates. The gel exhibited suitable characteristics for topical application such as clear texture, neutral odor, appropriate pH (5.1–5.6), and viscosity (26,000–58,000 ​Pa ​s). It also showed excellent spreadability, homogeneity, minimal irritancy, and pseudo plastic behaviour with sustained drug release (up to 94%) over 24 ​h. Stability testing and acute toxicity studies confirmed the safety and efficacy of the gel, while anti-inflammatory activity was demonstrated through carrageenan-induced rat paw edema model. The findings suggest that this curcumin-loaded gelatine ethosomal gel holds promise in revolutionizing inflammation therapy by improving efficacy, patient compliance, stability, controlled release, and bioavailability, thereby paving the way for innovative approaches in inflammation management.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100098"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145527902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Physiologically based pharmacokinetic (PBPK) modeling of drug-drug interactions between suraxavir marboxil and CYP3A4 inhibitors: Quantitative prediction of pharmacokinetic effects on active metabolite GP1707D07 苏拉沙韦玛博西和CYP3A4抑制剂之间药物相互作用的基于生理的药代动力学(PBPK)建模:对活性代谢物GP1707D07的药代动力学影响的定量预测
Pharmaceutical Science Advances Pub Date : 2025-12-01 Epub Date: 2025-09-25 DOI: 10.1016/j.pscia.2025.100095
Lan Yang , Fan Yang , Chao-Zhuang Shen , Yan-Xin Wang , Xiao-Lin Wang , Lang lv , Yue-E Wu , Pan-Pan Ye , Bo-Hao Tang , Guo-Xiang Hao , Shou-Sheng Yan , Wei Zhao , Yi Zheng
{"title":"Physiologically based pharmacokinetic (PBPK) modeling of drug-drug interactions between suraxavir marboxil and CYP3A4 inhibitors: Quantitative prediction of pharmacokinetic effects on active metabolite GP1707D07","authors":"Lan Yang ,&nbsp;Fan Yang ,&nbsp;Chao-Zhuang Shen ,&nbsp;Yan-Xin Wang ,&nbsp;Xiao-Lin Wang ,&nbsp;Lang lv ,&nbsp;Yue-E Wu ,&nbsp;Pan-Pan Ye ,&nbsp;Bo-Hao Tang ,&nbsp;Guo-Xiang Hao ,&nbsp;Shou-Sheng Yan ,&nbsp;Wei Zhao ,&nbsp;Yi Zheng","doi":"10.1016/j.pscia.2025.100095","DOIUrl":"10.1016/j.pscia.2025.100095","url":null,"abstract":"<div><div>Suraxavir marboxil (GP681) is a promising novel prodrug influenza polymerase acidic (PA) inhibitor whose active metabolite, suraxavir (GP1707D07), is primarily metabolized by cytochrome P450 3A4 (CYP3A4), raising concerns about drug-drug interactions (DDI) with CYP3A4 inhibitors. Traditional DDI assessment methods are limited for evaluating all potential combinations. This study aimed to develop a physiologically based pharmacokinetic (PBPK) model to predict the DDI risk between GP681 and CYP3A4 inhibitors of varying potency. The model was developed based on physicochemical and in vitro parameters, as well as clinical data, including a phase I single ascending dose study of GP681 tablets and a single-center phase I study evaluating the DDI between GP681 and strong CYP3A4 inhibitor itraconazole. The model was successfully verified against clinical data, with predicted-to-observed ratios for GP1707D07 exposure under itraconazole co-administration of AUC and C<sub>max</sub> of 1.042 and 1.357, respectively. Simulations using the validated model predicted a substantial increase in GP1707D07 exposure when co-administered with moderate inhibitors fluconazole (AUC ratio 2.820; C<sub>max</sub> ratio 1.509) and verapamil (AUC ratio 2.347; C<sub>max</sub> ratio 1.645), comparable to the effect of itraconazole. Weak inhibitors showed negligible effects. Consequently, clinical monitoring and potential dose adjustment of GP681 are recommended when co-administered with strong inhibitors and the moderate inhibitors. The study demonstrates the utility of PBPK modeling for efficient and predictive DDI assessment of complex prodrug systems, guiding the safe clinical use of GP681.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100095"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Protective activity of Basella alba l. Leaf extract on cardiac injury markers following intestinal ischemia-reperfusion: potential for cardiovascular therapy 白底菇叶提取物对肠缺血再灌注后心脏损伤标志物的保护作用:心血管治疗的潜力
Pharmaceutical Science Advances Pub Date : 2025-12-01 Epub Date: 2025-07-21 DOI: 10.1016/j.pscia.2025.100083
Olubayode Bamidele , Oyinkansola Fasipebi , Eniola E. Tomoloju , Lawrence D. Adedayo , Ayodeji F. Ajayi , Ayobami O. Afolabi
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