Drug Design, Development and Therapy最新文献

{"title":"Role of Radioiodine in Cancer Therapy: A Review of the Design and Challenges in Selecting Radioligands from Natural Sources.","authors":"Taufik Muhammad Fakih, Dhania Novitasari, Mukh Syaifudin, Edy Meiyanto, Okid Parama Astirin, Amirah Mohd Gazzali, Muchtaridi Muchtaridi","doi":"10.2147/DDDT.S524612","DOIUrl":"10.2147/DDDT.S524612","url":null,"abstract":"<p><p>The use of radioactive isotopes in cancer treatment has marked a pivotal shift in modern medicine, where precise diagnosis and targeted therapy now blend to offer patients more effective care with minimized side effects. Despite significant advancements, the exploration of iodine-labeled radioligands from natural sources remains underdeveloped, and comprehensive evaluations of their design, pharmacokinetics, and clinical relevance are still lacking. This gap has created a pressing need for systematic studies that bridge natural product chemistry with radiopharmaceutical applications. Since the initial application of iodine-131 in thyroid treatments, radioisotopes such as iodine-125 and iodine-131 have gained prominence in oncology due to their dual functionality: they enable accurate imaging while delivering therapeutic radiation directly to tumor cells, reducing harm to surrounding healthy tissues. Recent advancements in radiopharmaceuticals, particularly iodine-labeled compounds, aim to further improve this balance by enhancing cancer treatment efficacy and safety. This review synthesizes findings from clinical and experimental studies that explore a range of iodine-labeled compounds, including natural agents like hypericin, curcumin, and piperine, as well as various synthetic analogs. Key methodologies for incorporating iodine, such as the Iodogen method and other stable-labeling techniques, are evaluated for their impact on the compounds' pharmacokinetics, stability, and therapeutic performance. Furthermore, in silico methods are highlighted for their contribution to optimize the molecular structures, binding affinities, and specificity, streamlining the selection of high-potential candidates for radiopharmaceutical applications. Findings reveal that iodine-labeled compounds effectively concentrate in tumor cells, enhancing selectivity and reducing radiation exposure to non-cancerous tissues. Notably, these compounds demonstrate stability in biological environments, making them viable options for integrated diagnostic and therapeutic purposes. Moving forward, the ongoing refinement of compound stability and targeted biodistribution is crucial in ensuring these therapies can meet the demands of precision oncology and improve clinical outcomes across various cancer types.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8009-8039"},"PeriodicalIF":5.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Idebenone: Clinical Potential Beyond Neurological Diseases.","authors":"Bin Yi, Jun Zeng, Jiashuo Li, Kunfeng Liu, Xiaocheng Zhu, Xiang Chen, Yang Gao","doi":"10.2147/DDDT.S515053","DOIUrl":"10.2147/DDDT.S515053","url":null,"abstract":"<p><p>Idebenone, a short-chain analog of coenzyme Q10 with a hydroxydecyl side chain, is known to activate mitochondrial function by transferring electrons to the electron transport chain complex III, thereby promoting adenosine triphosphate production. Numerous clinical trials have demonstrated the effectiveness of idebenone in the treatment of neurological diseases. Interestingly, emerging evidence suggests that idebenone may also have beneficial effects beyond neurological conditions through disrupting mitochondrial membrane potential, inducing mitochondrial apoptosis, promoting mitophagy attenuating ferroptosis, reducing reactive oxygen species and lipid peroxidation, etc. This study aims to comprehensively review the clinical potential of idebenone in various fields, including cancers (such as breast cancer, melanoma, glioblastoma, neuroblastoma, hepatocellular carcinoma, prostatic carcinoma and pancreatic carcinoma), cardiovascular diseases (including atherosclerosis, hypertension, myocardial infarction and heart failure), diabetes mellitus, liver diseases, urogenital diseases, sepsis, and other diseases. The findings highlight the potential of idebenone as a promising therapeutic option for the prevention and management of these condition, which need to be validated in more clinical trials.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7929-7946"},"PeriodicalIF":5.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic and Safety Profiles of MIT-001, a Novel Ferroptosis Inhibitor, After Subcutaneous Administration in Healthy Participants.","authors":"Sujong Lee, Sungyeun Bae, Kyung-Sang Yu, SeungHwan Lee","doi":"10.2147/DDDT.S541415","DOIUrl":"10.2147/DDDT.S541415","url":null,"abstract":"<p><strong>Purpose: </strong>MIT-001 is a novel ferroptosis inhibitor with therapeutic potential for oxidative stress-related diseases. This study aimed to evaluate the pharmacokinetic (PK) and safety profiles of MIT-001 after subcutaneous (SC) administration in healthy participants.</p><p><strong>Methods: </strong>A randomized, double-blind, placebo-controlled, dose-escalation study was conducted in two parts: single ascending dose (SAD) and multiple ascending dose (MAD) studies. In the SAD study, participants received a single SC dose of MIT-001 at 10, 20, or 40 mg, with the 40 mg cohort also receiving a single IV dose in a crossover manner. In the MAD study, participants received SC doses of 20 or 40 mg once daily for seven consecutive days. Safety and tolerability were assessed by monitoring adverse events (AEs), physical examinations, vital signs, and clinical laboratory tests.</p><p><strong>Results: </strong>A total of 40 participants completed the study, with 24 in the SAD study and 16 in the MAD study. MIT-001 was rapidly absorbed, reaching the maximum concentration at a median time of 1.5-2.5 h. Accumulation ratios after multiple SC administrations were 2.75-2.77. PK profiles were comparable between SC and IV formulations. The most common AEs were mild local reactions at the injection site, with no statistically significant differences in incidence across dose levels. No serious AEs were reported.</p><p><strong>Conclusion: </strong>The systemic exposure of MIT-001 after SC administration increased linearly across the dose levels of 10-40 mg. MIT-001 was well tolerated after a single SC dose of 10-40 mg and multiple SC doses of 20-40 mg in healthy participants.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7999-8008"},"PeriodicalIF":5.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Yangweishu Ameliorates Chronic Atrophic Gastritis with Stomach Yin Deficiency Syndrome Through IL-6/STAT3 Signaling Pathway.","authors":"Zhiyong Jiao, Jia Zheng, Xinyu Yang, Qin Ruan, Yuhan Ma, Yuzhe Huang, Cheng Jin, Shuangying Gui, Zihua Xuan, Juan Liang, Xiaoyi Jia","doi":"10.2147/DDDT.S529330","DOIUrl":"10.2147/DDDT.S529330","url":null,"abstract":"<p><strong>Background: </strong>Chronic atrophic gastritis of stomach yin deficiency syndrome (YDCAG) is a precancerous lesion characterized by inflammation of gastric mucosa and atrophy of gastric adenocytes. Yangweishu (YWS) is widely used to treat gastrointestinal diseases.</p><p><strong>Objective: </strong>This study was to investigate the mechanism of YWS in YDCAG.</p><p><strong>Methods: </strong>The YDCAG rat model was established using a comprehensive modeling approach, and a human gastric epithelial cell (GES-1) injury model was induced by MNNG stimulation. Hematoxylin-eosin staining (HE), enzyme-linked immunosorbent assay (ELISA), real-time polymerase chain reaction (RT-PCR), immunohistochemistry and Western blotting were performed to observe the effects of YWS on YDCAG rats and GES-1 cells. Network pharmacology was conducted to identify potential core targets and signaling pathways involved in the anti-YDCAG effects of YWS. RT-PCR and Western blotting were employed to measure the gene and protein expression in the IL-6/STAT3 signaling pathway in vivo and in vitro. Apoptosis in GES-1 cells was evaluated through flow cytometry, immunofluorescence, RT-PCR, and Western blotting.</p><p><strong>Results: </strong>YWS significantly improved gastric morphology in YDCAG rats and alleviated GES-1 cell injury induced by MNNG. YWS treatment also reduced serum, tissue, and cellular levels of inflammatory cytokines, while enhancing antioxidant capacity. Network pharmacology analysis suggested that YWS modulates apoptosis and inhibits the IL-6/STAT3 signaling pathway. Furthermore, YWS has an ameliorative effect on apoptosis and inhibits the expression of IL-6/STAT3 signaling pathway genes and proteins in vitro and in vivo.</p><p><strong>Conclusion: </strong>YWS has a good therapeutic effect on YDCAG, which may be closely related to the inhibition of IL-6/STAT3 signaling pathway.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7865-7885"},"PeriodicalIF":5.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allicin Aplealleviates Gouty Arthritis by Regulating the Gut-Joint Axis, Reducing XOD Activity, Inhibiting Oxidative Stress, and Suppressing NLRP3 Inflammasome Activation.","authors":"Hao Wu, Mi-Mi Pang, Yao-Lei Li, Jia-Hui Hong, Pan-Miao Liu, Meng Bian, Jian-Jun Yang","doi":"10.2147/DDDT.S540116","DOIUrl":"10.2147/DDDT.S540116","url":null,"abstract":"<p><strong>Background: </strong>Gouty arthritis (GA) is a common joint inflammation closely related to hyperuricemia and urate crystal deposition, and its incidence is on the rise worldwide. Allicin, the primary biologically active component found in freshly crushed garlic extracts, has been reported to possess many beneficial biological functions.</p><p><strong>Methods: </strong>An animal model was used to evaluate the efficacy of allicin on GA rats, and 16S rRNA sequencing and metabolomics were used to explore changes in the gut microbiota and metabolites. Fecal microbiota transplantation (FMT) and fibroblast-like synoviocytes (FLS) used to explore the mechanism of allicin treating GA.</p><p><strong>Results: </strong>The results showed that allicin effectively improved the general state of GA rats, inhibited XOD activity, and significantly reduced ROS production and activation of the NLRP3 inflammasome, thereby exerting therapeutic efficacy to protect the kidneys and joints. Examination of the gut microbiota showed that the composition of the gut microbiota of GA rats improved after allicin treatment (increase in <i>Lactobacillus</i>). Metabolomic analysis revealed a significant increase in gut microbial short-chain fatty acid metabolites (butyric acid) following allicin treatment. Furthermore, FMT confirmed that allicin significantly alleviated GA and increased butyric acid content in a gut microbe-dependent manner. Finally, the role of butyric acid in inhibiting ROS generation and NLRP3 inflammasome activation in FLS was elucidated.</p><p><strong>Conclusion: </strong>This study highlights allicin as a promising therapeutic candidate for GA, emphasizing its potential to inhibit oxidative stress and inflammatory responses by regulating the gut-joint axis.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7887-7907"},"PeriodicalIF":5.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Health Technology Assessment: Evaluation of Monoclonal Antibodies for the Treatment of Neuromyelitis Optica Spectrum Disorders.","authors":"Changsheng Wang, Hanbiao Wu, Yeqing Huang, Aiqun Liu, Sha Lai","doi":"10.2147/DDDT.S535347","DOIUrl":"10.2147/DDDT.S535347","url":null,"abstract":"<p><strong>Objective: </strong>To systematically evaluate the clinical value of monoclonal antibodies for neuromyelitis optica spectrum disorders (NMOSD), a multidimensional assessment of three monoclonal antibody therapies (eculizumab, inebilizumab, and satralizumab) was conducted using the updated drug evaluation framework from the Rapid Guide for Drug Evaluation and Selection in Chinese Medical Institutions (2nd Edition). This study aims to provide evidence-based guidance for optimizing monoclonal antibody selection in clinical practice.</p><p><strong>Methods: </strong>A quantitative scoring system was employed across five distinct domains: pharmacological properties (28 points), efficacy (27 points), safety (25 points), economics (10 points), and other attributes (10 points).</p><p><strong>Results: </strong>The comprehensive evaluation scores, with a maximum of 100 points, were as follows: eculizumab (70.43), satralizumab (69.33), and inebilizumab (68).</p><p><strong>Conclusion: </strong>Eculizumab is strongly endorsed as the first-line therapeutic option due to its optimal benefit-risk profile. Satralizumab and inebilizumab may be considered as conditional alternatives, contingent upon institutional resources and individual patient factors. This tiered recommendation framework facilitates adaptive formulary management that aligns with the evolving therapeutic landscape and socioeconomic conditions, thereby providing a replicable model for healthcare systems worldwide.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7909-7927"},"PeriodicalIF":5.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic and Pharmacodynamic Interaction of Metformin and Ojeok-san in Healthy Volunteers.","authors":"Sooyoung Lee, Sumin Chae, Minji Kwon, Wang-Seob Shim, Kyung-Tae Lee, Sung-Vin Yim, Bo-Hyung Kim","doi":"10.2147/DDDT.S526915","DOIUrl":"10.2147/DDDT.S526915","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to evaluate the pharmacokinetics and pharmacodynamics of metformin and Ojeok-san (OJS) co-administration to healthy volunteers compared to those with metformin alone.</p><p><strong>Methods: </strong>This was an open-label, one-sequence, crossover study, with two 2-day hospitalization schedules lasting up to 14 days. Metformin was administered once daily on days 1 and 2. OJS was administered alone three times a day on days 3-7 and co-administered with metformin once a day on days 8 and 9. Plasma concentrations of metformin were measured using a validated LC-MS/MS method. To evaluate pharmacodynamics, oral glucose tolerance tests (OGTTs) were performed on days 1, 2, 8 and 9.</p><p><strong>Results: </strong>Fifteen participants were enrolled. The coadministration decreased C_max (1757.7 to 1668.9 ng/mL) and AUC_last (10407.4 to 9901.1 ng·h/mL), compared to those with metformin alone. Geometric mean ratios (90% Confidence Interval) of C_max and AUC_last between the co-administration with OJS and metformin alone were 92.15% (82.79-102.57) and 94.57% (85.6-104.48), respectively. Co-administration with OJS did not significantly change the mean glucose level compared to that with metformin alone.</p><p><strong>Conclusion: </strong>Co-administration with OJS decreased the plasma concentrations of metformin compared to that with metformin alone. However, the degree of decrease was not significant based on the geometric mean of the C_max and AUC_last. Considering the OGTT results, these changes in metformin concentration did not affect glucose concentration. In addition, there were no significant findings regarding safety profiles.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7825-7836"},"PeriodicalIF":5.1,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12423445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High Stability and Low Irritation of Enrofloxacin-Colistin Combination Injection Through a Tripartite Strategy.","authors":"Liyan Jia, Kaixiang Zhou, Xuechun Zhang, Xing Gao, Jijun Kang, Jianzhong Shen, Kui Zhu","doi":"10.2147/DDDT.S536132","DOIUrl":"10.2147/DDDT.S536132","url":null,"abstract":"<p><strong>Introduction: </strong>The rapid progression of bacterial resistance and the dearth of novel antimicrobial drug development impose a significant public health burden on the treatment of bacterial infections. Drug combination therapy has become an attractive strategy for combating multidrug-resistant bacterial infections. More importantly, matching the physicochemical properties of multiple components in formulations is essential for clinical application.</p><p><strong>Methods: </strong>First, an enrofloxacin-colistin combination injection was developed using a tripartite strategy, defined as a three-step process involving the conversion of enrofloxacin to its salt form, the addition of 1,2-propanediol, and pH adjustment. Second, independent gradient model based on Hirshfeld surface (IGMH), nuclear magnetic resonance (NMR), and ultraviolet-visible spectroscopy (UV-vis) analysis were used to investigate the molecular mechanism of this process. Finally, the irritancy, toxicity, and efficacy of the combination injection were evaluated in vivo and in vitro.</p><p><strong>Results: </strong>The tripartite strategy increased the solubility of enrofloxacin by 1500-fold from 0.18 mg/mL to 272.76 mg/mL, thereby preventing enrofloxacin precipitation during 6 months at both 30°C and 4°C, maintaining colistin stability, and reducing injection-site irritation. 1,2-Propanediol enhanced hydrogen bonding with enrofloxacin and inhibited its self-aggregation. Importantly, the combination injection exhibited no significant liver and kidney toxicity while demonstrating outstanding therapeutic efficacy against <i>Pasteurella multocida</i> pneumonia with 62.5% survival rate.</p><p><strong>Discussion: </strong>The limited solubility of enrofloxacin has long hindered its co-formulation with pH-sensitive drugs. The tripartite strategy establishes a paradigm for overcoming challenges related to the crystal precipitation of insoluble drugs and the pH limitations in complex formulations. Our findings demonstrate that the tripartite strategy effectively enhances the solubility, stability, and therapeutic efficacy of enrofloxacin-colistin combinations, offering a novel solution to overcome challenges in developing complex antibacterial formulations for veterinary use.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7809-7823"},"PeriodicalIF":5.1,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12423266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rheumatoid Arthritis Therapy Based on B Cells.","authors":"Yongqi Liang, Menglei Zha, Qifeng Liu, Zhifei Lai, Lei Li, Yiming Shao, Jianbo Sun","doi":"10.2147/DDDT.S527687","DOIUrl":"10.2147/DDDT.S527687","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent synovial inflammation, joint destruction, and progressive disability. While current therapeutic approaches-including corticosteroids, disease-modifying antirheumatic drugs (DMARDs), nonsteroidal anti-inflammatory drugs (NSAIDs), and biologic agents-provide symptomatic relief, their clinical utility remains constrained by substantial limitations such as systemic toxicity, drug resistance, and cumulative adverse effects. These challenges underscore the critical need for novel therapeutic strategies with improved safety and efficacy profiles. The pathogenesis of RA involves multifaceted immune dysregulation, with emerging evidence highlighting the central role of B lymphocytes in both disease initiation and progression. Although B cell-targeted therapies like rituximab demonstrate clinical efficacy, unanswered questions persist regarding the precise immune functions of B cell subpopulations in RA pathogenesis and their potential as translatable therapeutic targets. This comprehensive review examines the clinical burden of RA, limitations of conventional therapies, and the evolving understanding of B cell pathophysiology. We critically evaluate established B cell-directed interventions-including B cell depletion, B cell functional modulation, and regulatory B cell (Breg) promotion-while exploring innovative nanofabrication technologies that may overcome current therapeutic barriers. By synthesizing recent advances in immunomodulatory research, this analysis aims to inform future directions for targeted RA management.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7837-7852"},"PeriodicalIF":5.1,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12423268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevating Labor Analgesia: The Impact of Low-Dose Intrathecal Ropivacaine-Sufentanil in Combined Spinal-Epidural Analgesia: A Prospective Double-Blinded Randomized Trial.","authors":"Tianzhen Ji, Lei Xie, Tingyu Zhao, Zhengjie Chen, Xiaofen Sun, Yan Zhang, Cheng Xu","doi":"10.2147/DDDT.S532237","DOIUrl":"10.2147/DDDT.S532237","url":null,"abstract":"<p><strong>Background: </strong>Combined spinal-epidural (CSE) analgesia delivers rapid labor pain relief, yet high intrathecal opioid doses carry adverse effects, and ultra-low doses shorten block duration. Whether a low intrathecal dose of ropivacaine-sufentanil within CSE reduces clinician-delivered rescue boluses, compared with epidural analgesia (EA) or dural-puncture epidural (DPE), remains unclear.</p><p><strong>Methods: </strong>Laboring women requesting neuraxial analgesia were randomized to three groups: EA, DPE, and CSE. In the CSE group, analgesia was initiated with 2 mL of solution (1 mL 0.1% ropivacaine plus 1 mL containing 1 μg sufentanil), while the EA and DPE groups received 15 mL of 0.09% ropivacaine with 0.4 μg/mL sufentanil. The primary outcome was the proportion of patients requiring supplemental provider-administered analgesia for breakthrough pain. Secondary outcomes included analgesia onset time, VAS scores at multiple time points, patient-controlled epidural analgesia button presses, and cumulative analgesic consumption.</p><p><strong>Results: </strong>A total of 131 women completed the study: 42 (EA), 44 (DPE), and 45 (CSE). After adjusting for age, gestational age, cervical dilation, ASA status, BMI, and baseline VAS, the CSE group showed a significantly lower need for supplemental analgesia compared to EA (22% vs 48%; adjusted odds ratio [aOR]: 0.29, 95% CI: 0.10-0.78; P=0.013). The DPE group (30%) also exhibited a lower incidence than EA, but the difference did not reach significance (aOR: 0.43, 95% CI: 0.16-1.09; P=0.09). Between CSE and DPE, no significant difference emerged (aOR: 0.66, 95% CI: 0.24-1.74; P=0.27). The primary hypothesis that CSE would outperform both EA and DPE was not fully supported. For secondary outcomes, the CSE group demonstrated faster onset and significantly lower VAS scores at prespecified intervals than DPE and EA (P<0.001).</p><p><strong>Conclusion: </strong>Low-dose intrathecal ropivacaine-sufentanil CSE reduced supplemental analgesia needs versus EA but not DPE. Although CSE produced a faster onset and greater sensory block, its superiority over DPE was not established. Thus, CSE and DPE are clinically acceptable, with CSE potentially favored where minimal breakthrough pain is prioritized; further multicenter studies are warranted to confirm these findings.</p><p><strong>Trial registration number: </strong>ChiCTR2300076206. The trial is publicly available and is registered at www.chictr.org.cn on Sept 7, 2023.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7763-7775"},"PeriodicalIF":5.1,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12421255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}