Drug Design, Development and Therapy最新文献

{"title":"Effects of Dexmedetomidine on Postoperative Quality of Recovery and Electroencephalogram in Elderly Patients Undergoing Total Knee Arthroplasty: A Randomized Clinical Trial.","authors":"Hao Zhang, Yang Gao, Deng Liu, Wenhui Lyu, Xinyi Xing, Ziqing He, Lei Wang, Lei Zhang, Lijian Chen","doi":"10.2147/DDDT.S536217","DOIUrl":"10.2147/DDDT.S536217","url":null,"abstract":"<p><strong>Purpose: </strong>Anesthesia management strategies in elderly patients undergoing total knee arthroplasty (TKA) are critical to the postoperative quality of recovery (QoR), and changes in electroencephalogram (EEG) associated with anesthesia drugs may play an important role in this process. This study aimed to determine the effects of different doses of dexmedetomidine on postoperative QoR in elderly TKA patients, and whether there is a correlation with specific EEG changes.</p><p><strong>Methods: </strong>In this randomized controlled trial, elderly patients (aged ≥ 60 years) undergoing elective TKA were randomly allocated in a 1:1:1 ratio to 0.6 μg/kg/h dexmedetomidine (Group D2), 0.3 μg/kg/h dexmedetomidine (Group D1) and saline (Group N). On postoperative days 1 and 3, the15-item Quality of Recovery (QoR-15) scale was used to evaluate the postoperative recovery of patients among the three groups. Perioperative EEG data were also recorded.</p><p><strong>Results: </strong>The difference of QoR-15 scores on postoperative day 1 was significant for Group D2 vs Group N (126 [123-129] points vs 120 [116-123] points; median difference, 6 points [95% CI, 4 to 8]; <i>P</i> < 0.001) and Group D2 vs Group D1 (126 [123-129] points vs 122 [118-126]; median difference, 4 points [95% CI, 2 to 5]; <i>P</i> = 0.001), but not for Group D1 vs Group N. However, no significant difference was observed in the global and dimensional QoR-15 scores on postoperative day 3 among the three groups. Intraoperative EEG power spectra analysis revealed a decrease in α oscillation peak power and an increase in slow oscillation peak power in Group D1 and Group D2, compared with Group N. In addition, the slow oscillation peak power exhibited weak positive correlations with QoR-15 scores on postoperative day 1 (r = 0.319, P < 0.001).</p><p><strong>Conclusion: </strong>A loading dose of dexmedetomidine (0.5 μg/kg) infused within 10 minutes before anesthesia induction, followed by a maintenance at 0.6 μg/kg/h, improved QoR-15 on postoperative day 1 in elderly TKA patients, which may be partly related to the fact that dexmedetomidine deepens anesthesia by increasing the slow oscillation peak power in the appropriate range.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7467-7479"},"PeriodicalIF":5.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991404","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":"Mechanisms of Magnoliae Officinalis Cortex Volatile Oil in Alleviating 5-Fluorouracil-Induced Mucositis via Multi-Omics Approaches.","authors":"Jing-Nan Zhang, Ke-Di Li, Zhang-Jing Cao, Li-Yue Xu, Xiao-Lan Zhao, Fei Tang, Fu Peng, Cheng Peng, Hui Ao","doi":"10.2147/DDDT.S515605","DOIUrl":"10.2147/DDDT.S515605","url":null,"abstract":"<p><strong>Purpose: </strong>Chemotherapy-induced mucositis (CIM) causes severe gastrointestinal symptoms in cancer patients. Magnoliae Officinalis Cortex, a traditional medicine, has demonstrated therapeutic promise in mitigating intestinal mucositis and gastrointestinal disorders, with advantages including marked efficacy and low adverse effect profiles compared to conventional pharmacotherapies. However, the therapeutic potential and mechanisms of the volatile oil of Magnoliae Officinalis Cortex (MagO) against CIM remain elusive. This study aimed to investigate the protective effects and mechanisms of MagO against 5-Fluorouracil (5-FU)-induced mucositis in mice via integrated multi-omics approaches.</p><p><strong>Methods: </strong>CIM model was established in ICR mice via intraperitoneal injection of 5-FU. The therapeutic effect of MagO on 5-FU-induced CIM was evaluated by monitoring body weight, diarrhea score, spleen index, ileum histopathology, and measuring DAO, D-LA, and inflammatory cytokines levels in serum. Metabolites and gut microbiota were analyzed through non-targeted metabolomics and 16S rDNA sequencing. Furthermore, potential mechanisms of MagO were assessed via GC-MS, network pharmacology, molecular docking, Western blot, and RT-qPCR.</p><p><strong>Results: </strong>MagO ameliorated 5-FU-induced intestinal mucosal injury and barrier dysfunction, as evidenced by significantly increased body weight rate reduced diarrhea scores, and alleviated ileum tissue damage. It also decreased IL-1β, IL-6, TNF-α, D-LA, and DAO levels in serum. Furthermore, MagO restored gut microbiota composition and metabolite profiles, specifically modulated the arachidonic acid metabolism by promoting PGE2 synthesis and upregulating EP2 and EP4 expressions. Mechanistic studies demonstrated that MagO exerted anti-CIM effects through inhibition of the PI3K/AKT signaling pathway, upregulation of Bcl-2 and intestinal barrier proteins (ZO-1, Occludin) expressions, and downregulation of Bax expression.</p><p><strong>Conclusion: </strong>MagO mitigated CIM by modulating the PI3K/AKT signaling pathway and the PGE2/EP2/EP4 axis, restoring gut microbiota and metabolites composition, reducing apoptosis, and improving intestinal permeability.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7503-7525"},"PeriodicalIF":5.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991579","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":"Effect of Stellate Ganglion Block on Preventing Atrial Fibrillation After Esophagectomy: A Double-Blind Randomized Controlled Trial.","authors":"Tieshuai Liu, Jun Zhang, Jingwen Liang, Raojun Luo, Ziming Zhang, Jiwen Li, Zhichao Ai, Jiaqi Xiong, Shameera Sayer, Qihong Shen, Xin Yu, Gang Chen","doi":"10.2147/DDDT.S538004","DOIUrl":"10.2147/DDDT.S538004","url":null,"abstract":"<p><strong>Background: </strong>Postoperative atrial fibrillation (POAF) is a common complication after esophagectomy and is associated with adverse outcomes. This study investigated whether preoperative stellate ganglion block (SGB) could reduce the incidence of POAF and improve postoperative recovery.</p><p><strong>Methods: </strong>In this single-center, randomized, double-blind, placebo-controlled trial, 100 patients undergoing esophagectomy were randomly assigned to receive ultrasound-guided right-sided SGB with 7 mL of either 0.5% ropivacaine (SGB group) or normal saline (control group). The primary outcome was the incidence of POAF within 72 hours postoperatively. Secondary outcomes included the timing and duration of POAF, heart rate variability, other arrhythmias, sufentanil consumption, pain scores, vital signs, sleep quality, gastrointestinal recovery, length of hospital stay, complications and mortality.</p><p><strong>Results: </strong>The incidence of POAF was 10% in both groups (OR = 1.0, 95% CI: 0.27-3.69, <i>p</i> > 0.99). However, patients in the SGB group experienced significantly fewer premature atrial contractions (97 vs 347; <i>p</i> = 0.038), lower pain scores (VAS at rest: B = -0.60, <i>p</i> < 0.001; during movement: B = -0.67, <i>p</i> < 0.001) and lower heart rate on postoperative day 1 (B = -4.29, <i>p</i> = 0.026). Regarding gastrointestinal recovery, the SGB group showed significantly shorter times to first flatus (<i>p</i> = 0.001) and first semi-liquid intake (<i>p</i> = 0.027). Sleep disturbances were also less frequent in the SGB group (4% vs 21%, OR = 0.08, <i>p</i> = 0.039). No significant differences were observed between the groups in terms of length of hospital stay, incidence of postoperative complications or mortality.</p><p><strong>Conclusion: </strong>Although SGB did not reduce the incidence of POAF, it was associated with improved postoperative recovery. These findings suggest that SGB may serve as a beneficial adjunct to optimize recovery following esophagectomy.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7481-7492"},"PeriodicalIF":5.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991465","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":"Transformative Role of Artificial Intelligence in Drug Discovery and Translational Medicine: Innovations, Challenges, and Future Prospects.","authors":"Grace Edet Bassey, Ernest Aniefiok Daniel, Kazeem Bidemi Okesina, Adeyemi Fatai Odetayo","doi":"10.2147/DDDT.S538269","DOIUrl":"10.2147/DDDT.S538269","url":null,"abstract":"<p><strong>Introduction: </strong>The use of Artificial intelligence in drug discovery is changing the field of Medicine across the world today positively. In this review, the role of AI in each focus area for the improvement of the drug development process, and its relevance in translational medicine is discussed.</p><p><strong>Materials and method: </strong>A systematic review was conducted by searching databases such as PubMed and Scopus, employing key terms like \"AI\" \"drug discovery\" \"machine learning\" \"clinical trials\" and \"translational medicine.\" Inclusion criteria focused on peer-reviewed studies published between 2014 and 2024 that specifically addressed the role of AI in drug development. Data extraction involved categorizing findings based on different phases of drug discovery.</p><p><strong>Results: </strong>The findings reveal that the use of AI lowers costs, shortens the time required for drug development, and enhances the predictive capability. AI technologies play an essential role in molecular modeling, drug design and screening, and the efficient design of clinical trials. However, some of the issues that remain include the quality of available data, issues of interpretability of the models, and the more critical issue of ethical considerations that need collective efforts on the development of associate regulatory policies.</p><p><strong>Conclusion: </strong>AI holds immense potential to dramatically change and transform the process of drug discovery and translational medicine while promoting accurate prevention and cures. However, it is also important to understand how to work with existing problems to make the best use of AI in healthcare. The roles of AI technologies are likely to grow in the development of the medical future, provide patients with better results, and stimulate the innovations in the field of the drug creation.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7493-7502"},"PeriodicalIF":5.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999957","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":"Low-Dose Alfentanil Effectively Reduces the ED50 of Remimazolam for Loss of Consciousness in Pediatric Patients Undergoing General Anesthesia: A Study Using Up-and-Down Sequential Allocation Method.","authors":"Xinyuan Shi, Fuxia Yi, Hongyi Xiao, Shiyu Yu, Xiaohan Sun, Yaxin Wei, Fangli Yue, Fanceng Ji","doi":"10.2147/DDDT.S532565","DOIUrl":"10.2147/DDDT.S532565","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the effects of low-dose alfentanil on the 50% effective dose (ED₅₀)/95% effective dose (ED₉₅) of remimazolam for successful loss of consciousness during general anesthesia in pediatric patients.</p><p><strong>Patients and methods: </strong>Fifty-two pediatric patients (aged 3-12, ASA I-II) scheduled for elective surgery were divided into two groups: Group A (n=24;alfentanil 5 μg kg^-1 + remimazolam 0.1 mg kg^-1) and Group C (n=28;saline + remimazolam 0.15 mg kg^-1). The MOAA/S scale was employed for assessment. To calculate the ED50, ED95 of remimazolam for inducing loss of consciousness in pediatric patients undergoing general anesthesia. Record the monitored values (MAP, HR, SpO₂) at different time points and the incidence of injection pain, hiccups, spontaneous movements, hypotension, bradycardia, respiratory depression, and overall adverse events.</p><p><strong>Results: </strong>In Group A, the ED₅₀ of remimazolam for loss of consciousness in pediatric patients was 0.212 mg kg^-1 (95% CI: 0.182 - 0.242 mg kg^-1), significantly lower than that in Group C (0.340 mg kg^-1, 95% CI: 0.295-0.388 mg kg^-1, P <0.001). Similarly, the ED₉₅ in Group A was 0.265 mg kg^-1 (95% CI: 0.237-0.413 mg kg^-1), significantly lower than that in Group C (0.434 mg kg^-1, 95% CI: 0.387-0.737 mg kg^-1, P <0.001). The overall incidence of adverse reactions was 8.3% in Group A, significantly lower than the 39.3% in Group C (P = 0.012). Compared with baseline values at T0, the MAP of pediatric patients in both groups decreased at T2 (P<0.05), but the reduction remained within 20% of the baseline values.</p><p><strong>Conclusion: </strong>Low-dose alfentanil (5 μg kg^-1) significantly reduces the ED₅₀ and ED₉₅ of remimazolam for successful loss of consciousness during paediatric general anaesthesia induction and decreases the incidence of adverse reactions during remimazolam induced sedation.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7459-7466"},"PeriodicalIF":5.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12405720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999923","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":"Effect of Ciprofol on Postoperative Cognitive Function in Patients Undergoing Cardiac Surgery with Cardiopulmonary Bypass: A Prospective, Randomized, Controlled Trial.","authors":"Jun Lu, Yewei Shi, Xin Lan, Guangling Tang, Yi Shao, Chao Chen, Xinglong Xiong, Dongxu Chen, Jing Shi","doi":"10.2147/DDDT.S536225","DOIUrl":"10.2147/DDDT.S536225","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the effects of ciprofol on postoperative cognitive function in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB).</p><p><strong>Patients and methods: </strong>A total of 138 patients who underwent cardiac surgery with cardiopulmonary bypass were included in this prospective, randomized, controlled study. Patients were randomized into two groups: the Ciprofol group (Group C) and the Propofol group (Group P). During anesthesia induction and maintenance, the patients in Group C received ciprofol, whereas those in Group P received propofol. The primary outcome measure was the incidence of postoperative delirium (POD), which was assessed twice daily for 7 days after surgery via either the Confusion Assessment Method (CAM) or the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Statistical analyses included chi-square tests for categorical outcomes and relative risk calculations for POD. Additionally, delirium subtypes were recorded. The incidence of postoperative cognitive dysfunction (POCD) was evaluated at 1 and 3 months after surgery using the Telephone Montreal Cognitive Assessment (T-MoCA). Furthermore, the occurrence of postinduction adverse events, including hypotension, bradycardia, and tachycardia, as well as the incidence of postoperative complications, were also documented.</p><p><strong>Results: </strong>POD occurred in 19/64 (29.69%) patients in the Ciprofol group and 34/65 (52.31%) patients in the Propofol group (RR = 0.57; 95% confidence interval = 0.37 to 0.88; <i>p</i> = 0.009). There was no significant difference in the incidence of POCD at 1 month (22.03% vs 26.62%, <i>p</i> = 0.547) or 3 months (16.25% vs 16.00%; <i>p</i> = 0.771) after surgery between the two groups.</p><p><strong>Conclusion: </strong>Ciprofol was found to decrease the incidence of POD in patients who underwent cardiac surgery with cardiopulmonary bypass. Nevertheless, no significant effect of this intervention on the incidence of POCD was demonstrated at either 1 or 3 months after surgery. A reduction in the incidence of delirium may be associated with improved postoperative recovery, shortened hospital stays, and a decrease in long-term cognitive impairments.</p><p><strong>Registration: </strong>The study had been registered in the Chinese Clinical Trials Registry (www.chictr.org.cn; Trial Identifier: ChiCTR2200061712).</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7541-7552"},"PeriodicalIF":5.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999953","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":"Effectiveness and Safety of Anlotinib-Related Therapeutic Regimens in Patients with Previously Immune Checkpoint Inhibitors-Treated Advanced NSCLC: A Real-World Exploratory Study.","authors":"Xue-Sen Fang, Tie-Song Zhang, Shao-Jun Li, Yun-Long Zhao, Jing-Bo Li, Hui Xia, Ren-Tao Wang","doi":"10.2147/DDDT.S535615","DOIUrl":"10.2147/DDDT.S535615","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to identify the effectiveness and safety of anlotinib-related therapeutic regimens in patients with previously immune checkpoint inhibitors (ICIs)-treated advanced non-small cell lung cancer (NSCLC).</p><p><strong>Methods: </strong>A total of 107 patients with previously ICIs-treated advanced NSCLC who received anlotinib-related regimens or single-agent chemotherapy in clinical practice were included in this study retrospectively. The anlotinib group (AG) included 54 patients who received anlotinib-related regimens, and the chemotherapy group (CG) consisted of 53 patients who received single-agent chemotherapy. This study retrospectively collected the efficacy and safety data during the patients' therapeutic process and performed regular follow-up to obtain long-term survival data. Clinical outcomes and safety profiles between AG and CG were analyzed and compared.</p><p><strong>Results: </strong>Best overall response of the 107 patients with previously ICIs-treated advanced NSCLC suggested that objective response rates of AG and CG were 24.1% and 11.3%, respectively; no statistically significant difference was observed (<i>P</i> = 0.084). Disease control rates were 79.6% and 54.7%, respectively (<i>P</i> = 0.006). Furthermore, the median PFS of AG and CG were 6.3 months (95% CI = 0.91-11.69) and 2.8 months (95% CI = 2.32-3.28), respectively, which showed a statistically significant difference (<i>P</i> = 0.002). The median OS in AG and CG were 16.1 months (95% CI = 12.28-19.92) and 10.1 months (95% CI = 3.99-16.21), respectively, which also exhibited a statistically significant difference (<i>P</i> = 0.015). Incidence of adverse reactions with all grades in AG and CG were 85.2% and 83.0%, respectively, grade ≥3 adverse reactions occurred in 40.7% and 45.3%, respectively. Common adverse reactions of patients in AG included fatigue, hypertension, nausea and vomiting, and hematologic toxicity, while patients in CG commonly experienced fatigue, hematologic toxicity, nausea and vomiting, and liver toxicity.</p><p><strong>Conclusion: </strong>Among patients with previously ICIs-treated advanced NSCLC, anlotinib-related therapeutic regimens demonstrated encouraging efficacy and a tolerable safety profile compared with the single-agent chemotherapy regimen. This conclusion still needs further validation in prospective clinical trials.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7527-7540"},"PeriodicalIF":5.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999892","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":"Molecular Pharmacological Interventions for Endometrial Cancer: A Comprehensive Review.","authors":"Wei Qin, Yazhou Qi, Qianwen Li, Bei Wang, Jingmiao Wang, Xueke Ge, Yanhong Li, Xinyue Zhang, Kuan Liu","doi":"10.2147/DDDT.S524181","DOIUrl":"10.2147/DDDT.S524181","url":null,"abstract":"<p><p>Endometrial cancer, a common malignancy of the female reproductive system, has a rising incidence and complex clinical management due to its diverse molecular subtypes. This review examines the molecular mechanisms underlying EC, particularly the roles of the Bcl-2 family in apoptosis regulation and estrogen receptor signaling in tumor progression. We explore pharmacological interventions targeting these pathways, including BH3 mimetics and selective estrogen receptor modulators, which show promise but face challenges such as resistance and adverse effects. Additionally, we highlight the potential of natural compounds like curcumin, paclitaxel, and Ganoderma lucidum polysaccharides as adjunctive therapies, demonstrating efficacy in preclinical studies and early-phase clinical trials. This review aims to provide insights into the development of personalized therapeutic strategies for EC and to identify opportunities for optimizing clinical outcomes in future treatments.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7381-7392"},"PeriodicalIF":5.1,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12399865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991648","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":"Discordance in Drug-Drug Interaction Alerts for Antidotes: Comparative Analysis of Electronic Databases and Interpretive Insights from AI Tools.","authors":"Thitipon Yaowaluk, Supawit Tangpanithandee, Pinnakarn Techapichetvanich, Phisit Khemawoot","doi":"10.2147/DDDT.S543827","DOIUrl":"10.2147/DDDT.S543827","url":null,"abstract":"<p><strong>Background: </strong>Drug-drug interactions (DDIs) are a critical clinical concern, especially when administering multiple medications, including antidotes. Despite their lifesaving potential, antidotes may interact harmfully with other drugs. However, few studies have specifically investigated DDIs involving antidotes.</p><p><strong>Purpose: </strong>This study evaluated potential DDIs between commonly prescribed medications and antidotes using two widely used electronic databases, along with artificial intelligence (AI) to assess the concordance between these platforms.</p><p><strong>Materials and methods: </strong>A descriptive analysis was conducted using 50 frequently prescribed medications from the ClinCalc DrugStats Database (2022) and major antidotes as reported by California Poison Control Center. Potential interactions were assessed using Micromedex and WebMD as electronic databases, and ChatGPT and Google Gemini as representative AI. DDI severity levels and documentation quality were recorded, and database/AI agreement was analyzed using the kappa statistic.</p><p><strong>Results: </strong>Overall, 154 potential DDI pairs were identified by the databases (Micromedex: 100, WebMD: 118). Nineteen DDIs were classified as severe by both databases. The overall agreement between databases was poor (kappa = -0.126, p = 0.008), indicating significant discrepancies in DDI severity classification. The main mechanisms associated with severe DDIs included serotonin syndrome and QT prolongation, with methylene blue and psychiatric medications being major contributors to severe DDIs. When evaluating the 19 severe DDIs from both databases, the AI models generally aligned with the more severe rating in cases of database discordance. The AI models' consensus was often supported by severity-oriented justifications, highlighting this as a conservative approach to resolving discordant DDI information.</p><p><strong>Conclusion: </strong>Numerous potential DDIs between prescribed drugs and antidotes were identified, with notable inconsistencies between the two databases and AI. This underscores the need to harmonize DDI evaluation criteria across drug information systems and promote clinicians' awareness of inter-database variability. Incorporating comprehensive DDI screening and shared decision-making is essential to ensure safe and effective patient care.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7427-7443"},"PeriodicalIF":5.1,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12399100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946576","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":"Mechanisms of Remifentanil-Induced Postoperative Hyperalgesia: A Comprehensive Review.","authors":"Kexin Zhu, Xiaolin Wen, Xuan Mei, Fang Fang, Tianyao Zhang","doi":"10.2147/DDDT.S550335","DOIUrl":"10.2147/DDDT.S550335","url":null,"abstract":"<p><p>Remifentanil, a widely used ultra-short-acting μ-opioid receptor agonist in clinical anesthesia, is strongly associated with postoperative hyperalgesia (remifentanil-induced hyperalgesia, RIH), posing significant challenges to postoperative pain management. RIH is characterized by an abnormally heightened pain perception following opioid withdrawal, and its underlying mechanisms are complex and multifactorial. Current research highlights the roles of central sensitization, peripheral sensitization, and multiple interacting molecular pathways. These include NMDA receptor activation, glial cell activation, neuroinflammation, disinhibition of inhibitory neurotransmission, and dysfunction of the descending pain modulation system. Additionally, alterations in ion channel expression, synaptic plasticity enhancement, and peripheral responses to inflammatory mediators contribute critically to RIH development. Individual factors such as age, sex, genetic polymorphisms, and surgical type significantly influence the risk of RIH. Although substantial progress has been made in elucidating the molecular mechanisms of RIH, a unified theoretical framework and effective clinical strategies remain lacking. Future studies should emphasize multi-omics approaches and clinically relevant experimental models to uncover key regulatory targets and provide a theoretical basis for individualized analgesic interventions.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7445-7457"},"PeriodicalIF":5.1,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991674","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}