Current drug metabolism最新文献

{"title":"Moonlighting Proteins: Unveiling Their Multifunctionality in Metabolic Regulation and Drug Discovery.","authors":"Shatrudhan Prajapati, Ajay Pal Singh, Namrata Bhadouria","doi":"10.2174/0113892002378207250709231938","DOIUrl":"https://doi.org/10.2174/0113892002378207250709231938","url":null,"abstract":"<p><p>Moonlighting proteins, defined by their ability to perform distinct, independent functions beyond their primary roles, have garnered attention in metabolic regulation and drug discovery. This review highlights the emerging significance of these proteins in diverse physiological and pathological processes. With exam-ples like glycolytic enzymes and Krebs cycle components, we explore their involvement in transcriptional regulation, immune responses, and stress modulation. Their unique ability to mediate host-pathogen interac-tions and disease progression underscores their potential as therapeutic targets. Advanced technologies, such as proteomics and bioinformatics, have revolutionized the identification and characterization of these proteins, unraveling their structural and functional complexities. This synthesis aims to bridge gaps in understanding protein multifunctionality and advocates its implications in drug development. By targeting specific functions of moonlighting proteins while preserving their essential roles, new strategies in pharmacology and personal-ized medicine are envisioned. The review also proposes a roadmap for leveraging these proteins' multifunc-tionality to address current challenges in therapeutic interventions.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral Metronomic Formulation of Carboplatin Loaded PEGylated- MWCNTs: HPLC Method Validation and Pharmacokinetic Studies in Rabbit's Plasma.","authors":"Suraj Sharma, Ketousetuo Kuotsu, Sweet Naskar","doi":"10.2174/0113892002378541250704181148","DOIUrl":"https://doi.org/10.2174/0113892002378541250704181148","url":null,"abstract":"<p><strong>Background: </strong>Carbon nanotubes (CNTs) have emerged as promising nanocarriers in drug delivery due to their unique physicochemical properties and biocompatibility.</p><p><strong>Objective: </strong>This study aims to explore the potential of oral sustained-release metronomic drug delivery formulations of carboplatin (CP), a widely used antitumor prodrug, utilizing carbon nanotubes as carriers.</p><p><strong>Methods: </strong>A comprehensive literature review was conducted using PubMed and Scopus databases, covering studies published between the years 2010 and 2024, focusing on CNT-based drug delivery systems and their application in cancer therapeutics.</p><p><strong>Results: </strong>CNTs have demonstrated significant potential in terms of high drug loading efficiency, targeted drug delivery, improved pharmacokinetics, and enhanced bioavailability. Several studies have also highlighted their utility in sustained and controlled drug release, which is critical for metronomic chemotherapy.</p><p><strong>Conclusion: </strong>Carbon nanotube-based drug delivery systems represent a promising platform for the development of oral sustained metronomic formulations of carboplatin. However, further research is needed to address concerns related to toxicity, biodegradability, and regulatory acceptance before clinical translation.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unexpected Clinically Significant Drug-Drug Interaction between Tacrolimus and Metronidazole in the Early Period after Renal Transplantation: A Literature Review.","authors":"Yun Xiao, Hua Zou, Xiaoyu Han, Chao Zheng, Chenglong Yin, Zhengyao Jiang, Sheng Zou, Anle Du, Na Deng, Guohui Li, Shuiwen Ye, Xiaohui Guo, Lin Zhong, Jiake He","doi":"10.2174/0113892002364104250701091104","DOIUrl":"https://doi.org/10.2174/0113892002364104250701091104","url":null,"abstract":"<p><strong>Introduction: </strong>Drug interactions necessitate careful consideration in clinical practice. It is imperative for clinicians and pharmacists to monitor drug exposure and the co-administration of medications promptly in order to avert adverse outcomes and achieve optimal efficacy.</p><p><strong>Objectives: </strong>The prevalence of oral lesions varies from 28% to 60% in the short term after renal transplantation. The clinical use of metronidazole in the treatment of anaerobic bacterial infections among solid organ transplant recipients has been complicated by the potentially significant and unpredictable drug-drug interactions.</p><p><strong>Methods: </strong>We present an unexpected, clinically significant drug-drug interaction between tacrolimus and metronidazole in the early period after renal transplantation and describe the potential mechanism and clinical characteristics of this drug-drug interaction through a literature review.</p><p><strong>Results: </strong>A 34-year-old female experienced a 65% increase in dose-normalized tacrolimus trough concentration after intravenous administration of metronidazole at 1000 mg/day for 8 days. When metronidazole was switched from intravenous to oral for 5 days, dose-normalized tacrolimus trough concentration was still increased by 52.4%. The magnitude of tacrolimus-metronidazole drug-drug interaction seems to be contingent upon the dose of metronidazole and the route of metronidazole administration. After cessation of metronidazole for one month, this drug-drug interaction, as assessed by weight-normalized tacrolimus dose, may still persist.</p><p><strong>Conclusion: </strong>In the early period following renal transplantation, the long-term concomitant use of metronidazole is likely to elevate the trough concentration of tacrolimus. Gene screening for CYP3A5*3/*3 and ABCB1 3435C>T in recipients of solid organ transplants may support individualized tacrolimus prescribing and facilitate the mitigation of risks associated with drug-drug interactions.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Magic of Drug Targeting Is \"Secretly\" Tied to Optimal Drug Distribution and Exposure.","authors":"Ming Hu","doi":"10.2174/0113892002423192250625041459","DOIUrl":"https://doi.org/10.2174/0113892002423192250625041459","url":null,"abstract":"","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comprehensive Review on the Pharmacokinetics and Bioanalysis of Piperaquine.","authors":"Yuewu Xie, Wenting Zhang, Ziqing Rui, Yuan Dai, Jie Xing, Jun Han","doi":"10.2174/0113892002374755250613064601","DOIUrl":"https://doi.org/10.2174/0113892002374755250613064601","url":null,"abstract":"<p><p>Piperaquine is an important partner drug in artemisinin-based combination therapy, which is highly effective for the treatment of uncomplicated malaria. Several studies have been reported on its pharmacoki-netic profiles in different populations, as well as its bioanalytical methods. Piperaquine shows a very large volume of distribution (up to 877 l/kg), a low oral clearance (0.3-1.9 l/h/kg), and an extremely long terminal elimination half-life (up to 30 days) in both healthy volunteers and malarial patients. Piperaquine metabolism is primarily mediated by CYP3A4, and to a lesser extent by CYP2D6 and CYP2C8. The oral bioavailability of piperaquine can be influenced by the consumption of high-fat food. The pharmacokinetics of piperaquine is affected by body weight, age, and pregnancy. Piperaquine has limited clinically relevant interactions with most commonly prescribed drugs. Plasma has been the most commonly studied matrix, and the most used pretreatment techniques involve protein precipitation. HPLC-UV and HPLC-MS/MS are usually used for the quantification of piperaquine in biological samples with researchers seeking a balance between affordability and sensitivity. This review summarizes the analytical assays used for the quantification of piperaquine in biological samples and its pharmacokinetic properties, with particular attention to information on food-drug interactions, drug-drug interactions, and pharmacokinetic characteristics in special populations, including pregnant women and children.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and Antimicrobial Activity of Silver/Copper Oxide/Clay Hybrid Nanocomposites Against Gram-Positive and Gram-Negative Bacteria.","authors":"Masoud Fardin, Narges Sadr, Amirmohammad Rezvani, Faezeh Hajhosseinjavaheri, Erfaneh Dalghi","doi":"10.2174/0113892002392051250612052515","DOIUrl":"https://doi.org/10.2174/0113892002392051250612052515","url":null,"abstract":"<p><strong>Background: </strong>The rapid surge in bacterial resistance to classical antibiotics and antimicrobial agents has driven researchers to identify new classes of antimicrobial agents. At the nanoscale, nanotechnological progress has strongly underscored the application of silver and copper since they present high antimicrobial activities toward gram-positive and gram-negative bacteria. Nanostructures containing these two elements-all the more so for hybrid nanocomposites-have been scantily the subject of investigated. The present work aims to develop and study a silver/copper oxide/clay hybrid nanocomposite.</p><p><strong>Methods: </strong>Nanocomposites of silver, copper oxide, and their hybrid with clay were synthesized via chemical precipitation under controlled pH (9-11) and temperature (60-90°C) conditions. The antibacterial activity was assessed using standard 0.5 McFarland-adjusted bacterial inocula. Characterization was performed using FTIR, XRD, FESEM, and TEM techniques. MIC and MBC were determined through serial dilution, and data were analyzed using one-way ANOVA and Tukey's test (SPSS v26).</p><p><strong>Results: </strong>The results indicated that the fabricated nanocomposite was impure, with nanosilver particles measuring 30-40 nm and copper oxide particles measuring 200-250 nm. The morphological properties of synthesized Ag/Cu2O/clay nanocomposites were evaluated using X-ray diffractometer analysis. The minimum inhibitory concentration (MIC) of the hybrid nanocomposite against Staphylococcus aureus and Bacillus subtilis was 1024 μg/ml, and for Escherichia coli and Pseudomonas aeruginosa 2048 μg/ml. The minimum bactericidal concentration (MBC) against Staphylococcus aureus and Bacillus subtilis was 4096 μg/ml, and for Escherichia coli 4096 μg/ml, and Pseudomonas aeruginosa 8192 μg/ml.</p><p><strong>Conclusion: </strong>These results showed that the antimicrobial property of silver/copper/clay hybrid nanocomposite was better than copper/silver and clay nanocomposite against gram-positive bacteria, while showing a similar effect against gram-negative bacteria.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HFD-induced Alterations in Renal Tubular Oatp4c1-P-gp Transport Systems in Mice: Impact on Digoxin Renal Excretion and Gadolinium-Enhanced Radiological Manifestations.","authors":"Jingwen Men, Jing Li, Tianyan Zhang, Yang Chen, Bin Xu, Huinan Hou, Lu Sun, Haoran Yue, Zhaoyue Duan, Ting Gui, Zhibo Gai","doi":"10.2174/0113892002371501250610074757","DOIUrl":"https://doi.org/10.2174/0113892002371501250610074757","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;The clearance of digoxin in obese patients with renal impairment is reduced, leading to elevated serum concentrations and increased risks of digoxin toxicity. However, the exact mechanism of such alterations in obese patients remains unclear. Previous studies have suggested that the organic anion transport-ing polypeptide 4c1 (Oatp4c1, Slco4c1) mediates the elimination of digoxin at the basal membrane of the proximal tubule (PT), indicating its potential role in the pharmacokinetic changes in obese patients. This study aims to investigate the effects of a high-fat diet on digoxin pharmacokinetics and transporter expression in mouse models and further analyze its significance by detecting the expression of transporters in human renal tissue samples.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;First, a high-fat diet (HFD)-induced obese mouse model was established. Mice were intraperitoneally injected with digoxin, and 24-hour urine samples and blood samples at five time points were collected. Pharmacokinetic evaluation was performed using liquid chromatography-tandem mass spectrometry. Renal pathological changes and the expression of digoxin transporters (Oatp4c1 and P-glycoprotein (P-gp)) were assessed using histological staining, Western blots (WB), as well as quantitative polymerase chain reaction (qPCR). Human renal pathologic alterations and expression of transporter proteins showed consistency with the results of animal experiments. To explore the potential use of gadolinium-ethoxybenzyl-diethylenetri-amine-pentaacetic acid (Gd-EOB-DTPA) as a marker for Oatp4c1 function, drug interactions between digoxin and Gd-EOB-DTPA were assessed in mice.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;HFD-induced obese mice showed significant increases in body weight, blood glucose, and triglyceride, along with elevated blood concentration of digoxin, increased areas under the curve, reduced renal clearance rate (CLr), and prolonged half-life (t1/2). Histological staining revealed proximal tubular epithelial cell detachment and slight fibrosis in the kidney of the HFD group, with decreased expression of villin, the protein marker for PT. Immunofluorescent staining and Western blots for digoxin transporters showed a significant reduction of Oatp4c1 and P-gp proteins, suggesting that the renal elimination of digoxin was affected solely by the reduced level of Oatp4c1 and P-gp proteins. Co-administration of digoxin and Gd-EOB-DTPA resulted in a reduced clearance of Gd-EOB-DTPA, suggesting that both share the same transporter. The blood concentration of Gd-EOB-DTPA was higher (77.5%) in the HFD group. Renal magnetic resonance imaging (MRI) intensity was lower in the HFD group after Gd-EOB-DATP administration compared to the Chow group.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Obesity-induced kidney damage results in decreased Oatp4c1 and P-gp expression and function in PT, resulting in a reduction of digoxin renal clearance. The inhibition of Gd-EOB-DTPA cleara","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Application of Artificial Intelligence in Drug ADME Research.","authors":"Jiayi Yin, Yuting Qi, Feng Zhu, Su Zeng","doi":"10.2174/0113892002398453250611101651","DOIUrl":"10.2174/0113892002398453250611101651","url":null,"abstract":"","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Effects of Oxidative Stress on Female Reproductive Function: The Role of Antioxidant Supplementation.","authors":"Dala N Daraghmeh, Sawsan Salameh, Massa Zahdeh, Rania Ghanem, Rafik Karaman","doi":"10.2174/0113892002357565250604075932","DOIUrl":"https://doi.org/10.2174/0113892002357565250604075932","url":null,"abstract":"<p><strong>Background: </strong>The female reproductive system is susceptible to oxidative stress, which can interfere with ovulation, menstrual cycles, egg quality, and tubal function, ultimately leading to infertility. Antioxidants might play a crucial role in protecting reproductive health by neutralizing Reactive Oxygen Species (ROS) and preventing cellular damage.</p><p><strong>Objective: </strong>To provide an overview of the research that has been performed on the benefits of antioxidant supplementation for increasing female fertility.</p><p><strong>Methods: </strong>We conducted a comprehensive search of PubMed, Embase, and Google for full-text, English-lan-guage publications between 2000 and 2023 that investigated the relationship between antioxidant supplemen-tation and improvements in female fertility.</p><p><strong>Results: </strong>Antioxidants have been investigated for their potential to improve fertility outcomes in subfertile women. Antioxidant supplementation shows promise in mitigating these effects by neutralizing excess ROS and restoring balance, leading to improved egg count and fertility outcomes. However, it is important to note that the effectiveness of antioxidant supplementation can vary depending on individual health factors and the specific antioxidants used. Studies suggest that a combination of antioxidants, such as vitamins C and E, se-lenium, and coenzyme Q10, may be more beneficial than single supplements. Although individual research has shown beneficial correlations between different antioxidant supplementation and female fertility, study repeatability is poor. As a result, further large-scale, well-designed clinical trials are necessary to better un-derstand the precise role and optimal combinations of antioxidants for enhancing fertility in subfertile women.</p><p><strong>Conclusion: </strong>This review study offers crucial insights into the complex connection between OS and female reproductive health. It highlights the potential advantages of antioxidant supplements as a preventative strat-egy. To enhance female fertility outcomes, further research, particularly randomized controlled clinical trials, is needed to determine best practices, identify populations that could benefit the most, and explore innovative antioxidant treatments.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Gut Microbial Transformation-Integrated Network Pharmacology Approach to Elucidate the Therapeutic Mechanisms of Timosaponin AIII in Diabetes.","authors":"Yingfeng Du, Huiyi Zhang, Jinhuan Wei, Xi Tian, Wenyu Li, Mengxin Yang, Qian Zhang, Nan Wang, Yiran Jin","doi":"10.2174/0113892002357684250527113902","DOIUrl":"https://doi.org/10.2174/0113892002357684250527113902","url":null,"abstract":"<p><strong>Objective: </strong>Timosaponin AIII, with poorly soluble characteristics, has a potential antidiabetic effect evaluated in vitro and in vivo. The major problem associated with poorly soluble drugs is very low bioavailability. This study aimed to investigate the metabolic profiles and antidiabetic mechanism of Timosaponin AIII.</p><p><strong>Materials and methods: </strong>The metabolic profiles of Timosaponin AIII in intestinal flora were analyzed using LC-MS/MS. Based on mass spectrometry analysis, network pharmacology combined with the GEO database was used to identify potential targets and elucidate the antidiabetic mechanism. Finally, the stability of compound-target complexes was further functionally confirmed by molecular docking.</p><p><strong>Results: </strong>As a result, 13 metabolites were identified. After the compound-target network, the genes of its metabolites increased by 60 compared to those of Timosaponin AIII. Subsequently, 13 core targets related to antidiabetic efficacy were identified through PPI network analysis. Key genes EGFR, MAPK1, and ICAM1 with strong binding efficiencies with metabolites were identified as crucial targets for the therapeutic effects of Timosaponin AIII. The KEGG analysis indicated that timosaponin AIII combated diabetes through various signaling pathways, including PI3K-Akt, FoxO, and HIF-1 signaling pathways, etc. Conclusions: Taken together, this study clarified the mechanism of Timosaponin AIII against diabetes by identifying additional targets and pathways, and the importance of glycosidic structures. Otherwise, we might provide a solid foundation for the development of clinical applications of Timosaponin AIII.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}