Drug Design, Development and Therapy最新文献

{"title":"Effects of Sodium Bicarbonate Ringer's Solution versus Lactate Ringer's Solution on Emergence Time in Patients Undergoing Supratentorial Tumor Resection: A Randomized Controlled Trial.","authors":"Jie Wang, Yechun Wang, Dutian Wang, Guoliang You, Min Wang, Xingzhi Liao, Lifei Tang","doi":"10.2147/DDDT.S646669","DOIUrl":"10.2147/DDDT.S646669","url":null,"abstract":"<p><strong>Background: </strong>In neuroanesthesia, a prompt emergence from anesthesia is essential for postoperative neurologic assessment. Intraoperative infusion of sodium bicarbonate Ringer's solution (BRS) and lactated Ringer's solution (LRS) have different effects on internal environment, potentially contributing to discrepant recovery profiles. Therefore, this study aimed to compare the recovery of BRS and LRS in patients undergoing craniotomy for supratentorial tumors.</p><p><strong>Methods: </strong>This randomized controlled trial enrolled patients undergoing elective supratentorial tumor resection. Patients were randomized to receive BRS or LRS for intraoperative fluid therapy. The primary outcome was emergence time. Secondary outcomes included extubation times, short Orientation Memory Concentration Test (SOMCT) at 15 min after extubation and postoperative complications. Parameters including lactic acid (Lac), pH, base excess (BE), and serum Mg²⁺ levels were measured at several time points and compared between the two groups. Total length of hospital stay was also recorded and compared between the two groups. Primary analysis followed the intention-to-treat (ITT) principle. A per-protocol (PP) sensitivity analysis was also performed for the primary outcome.</p><p><strong>Results: </strong>The ITT analysis included 100 patients (BRS group: n = 50; LRS group: n = 50). Following exclusions for short surgery or massive intraoperative blood loss, the PP set included 48 BRS and 47 LRS patients. In the ITT analysis, Patients assigned to the BRS group had shorter emergence (13min vs 16min; median difference, 3; 95% CI, 1 to 4; <i>P</i>=0.003) and extubation times (15min vs 18min; median difference, 2; 95% CI, 1 to 4; <i>P</i>=0.01), and lower lactate levels at the end of surgery and 0.5 hour after extubation (<i>P</i> < 0.05). SOMCT scores at 15 min after extubation, postoperative complications and total hospitalization days were comparable between the groups (<i>P</i> > 0.05). Additionally, no significant group-by-time interactions were found for pH, BE and Mg²⁺ levels, indicating similar temporal changes between groups (<i>P</i> > 0.05).</p><p><strong>Conclusion: </strong>Patients receiving BRS during supratentorial tumor resection had faster emergence and shorter extubation times, but similar SOMCT scores at 15 min after extubation and complication rates compared to those receiving LRS.</p><p><strong>Trial registration: </strong>Chinese Clinical Trial Registry, ChiCTR2500105691, registered on July 9, 2025.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"646669"},"PeriodicalIF":6.1,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179842","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":"Ilioinguinal-Transversus Abdominis Plane (I-TAP) Block with Liposomal Bupivacaine for Analgesia After Cesarean Delivery: A Randomized Controlled Trial.","authors":"Yun Pan, Xiaobing Hu, Xin Fang, Yu Zang, Yao Zhou, Fuyi Shen, Zhendong Xu","doi":"10.2147/DDDT.S640932","DOIUrl":"10.2147/DDDT.S640932","url":null,"abstract":"<p><strong>Purpose: </strong>Cesarean delivery is frequently associated with suboptimal postoperative analgesia. While PROSPECT guidelines recommend transversus abdominis plane (TAP) block for post-cesarean analgesia, conventional TAP block may provide incomplete coverage of the L1 dermatome, potentially limiting analgesia for lower abdominal incisions. This study evaluated the efficacy and safety of ultrasound-guided ilioinguinal-transversus abdominis plane (I-TAP) block with liposomal bupivacaine after cesarean delivery.</p><p><strong>Patients and methods: </strong>In this single-center, randomized controlled trial, 150 healthy parturients undergoing elective cesarean delivery under combined spinal-epidural anesthesia were allocated in a 1:1:1 ratio to I-TAP block, transversus abdominis plane (TAP) block, or sham block. The I-TAP and TAP blocks were performed using a mixture of 266 mg liposomal bupivacaine and 50 mg bupivacaine hydrochloride, diluted with 0.9% sodium chloride to a total volume of 60 mL. The primary outcome was the cumulative intravenous sufentanil consumption from the patient controlled intravenous analgesia (PCIA) device during the first 24 h after surgery. Secondary outcomes included 48 h PCIA sufentanil requirements, Quality of Recovery-15 (QoR-15) scores, pain scores, time to first rescue analgesia, time to ambulation, successful breastfeeding initiation, maternal satisfaction, and adverse events.</p><p><strong>Results: </strong>At 24 h postoperatively, the I-TAP group had significantly lower sufentanil consumption than the TAP group (mean difference -11.4 μg, 95% CI: -17.6 to -5.3; 37.1% reduction) and the control group (mean difference -23.2 μg, 95% CI: -29.4 to -17.1; 54.5% reduction) (both P < 0.001). This difference persisted at 48 h. The I-TAP group also had lower postoperative pain scores, higher QoR-15 scores, longer time to first opioid rescue request, higher maternal satisfaction and higher rate of successful breastfeeding initiation. Adverse events were similar among groups.</p><p><strong>Conclusion: </strong>Compared with TAP block plus epidural hydromorphone and epidural hydromorphone alone, liposomal bupivacaine I-TAP block combined with epidural hydromorphone significantly reduced post-cesarean PCIA sufentanil requirements, improved postoperative analgesia and recovery quality, and increased maternal satisfaction without evidence of increased adverse events. This technique may provide a safe and effective option for implementation within multimodal analgesic strategy after cesarean delivery.</p><p><strong>Clinical trial number and registry: </strong>ChiCTR2500112390.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"640932"},"PeriodicalIF":6.1,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179834","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":"A Comment on \"Liposomal Bupivacaine versus Bupivacaine Hydrochloride Plus Dexamethasone for Combined Adductor Canal and iPACK Blocks in Total Knee Arthroplasty: A Randomized Controlled Trial\" [Letter].","authors":"Chao Han, Jinyu Ji, Bo Chen","doi":"10.2147/DDDT.S660176","DOIUrl":"https://doi.org/10.2147/DDDT.S660176","url":null,"abstract":"","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"660176"},"PeriodicalIF":6.1,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179874","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":"Interpreting Model-Informed Recommendations for Initial Tacrolimus Dosing in Membranous Nephropathy [Letter].","authors":"Wenjing Fu, Jingyu Wang","doi":"10.2147/DDDT.S660429","DOIUrl":"https://doi.org/10.2147/DDDT.S660429","url":null,"abstract":"","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"660429"},"PeriodicalIF":6.1,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179944","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":"Liposomal Bupivacaine Combined with Bupivacaine vs Ropivacaine for Paravertebral Blockade in Single-Port Video-Assisted Thoracoscopic Surgery: A Propensity-Matched Comparison of Postoperative Opioid Use.","authors":"Wenchuan Guan, Guanyu Yang, Jing Sang, Liumei Li, Qinjun Chu","doi":"10.2147/DDDT.S642610","DOIUrl":"https://doi.org/10.2147/DDDT.S642610","url":null,"abstract":"<p><strong>Objective: </strong>To compare the effect of preoperative single-injection paravertebral block using liposomal bupivacaine/bupivacaine mixture versus ropivacaine on cumulative postoperative opioid consumption in patients undergoing thoracic surgery.</p><p><strong>Methods: </strong>This retrospective cohort study included adult patients who underwent elective single-port video-assisted thoracoscopic surgery (wedge resection, segmentectomy, or lobectomy) between January 2024 and February 2026. Patients received an ultrasound-guided single-injection paravertebral block with either 0.5% ropivacaine (20 mL) or a mixture of 1.3% liposomal bupivacaine (10 mL) and 0.5% standard bupivacaine (10 mL). The primary outcome was cumulative postoperative opioid consumption throughout the hospitalization, delivered via patient-controlled analgesia (PCA) and converted to oral morphine milligram equivalents. Secondary outcomes included pain scores, time to first PCA request, postoperative adverse events, and length of stay. Propensity score matching (1:2) was performed to balance baseline clinical and intraoperative characteristics.</p><p><strong>Results: </strong>Among 492 eligible patients, 331 received ropivacaine and 161 received liposomal bupivacaine/bupivacaine combination. After matching, 210 and 108 patients were included in the ropivacaine and liposomal bupivacaine groups, respectively. The median cumulative postoperative opioid consumption was lower in the liposomal bupivacaine group (92.1 mg [IQR, 59.1-122.3]) than in the ropivacaine group (226.2 mg [IQR, 170.2-260.0]), with a median difference of 128.2 mg (95% CI, 111.0-143.9; <i>P</i> < 0.001). The liposomal bupivacaine group was also associated with lower resting and movement pain scores at 24 and 48 hours postoperatively, a longer time to first PCA press (26.0 vs. 6.0 hours; <i>P</i> < 0.001), and a lower incidence of postoperative dizziness (21.3% vs. 34.3%; <i>P</i> = 0.017).</p><p><strong>Conclusion: </strong>For patients undergoing video-assisted thoracoscopic surgery, preoperative single-injection paravertebral blockade with liposomal bupivacaine/bupivacaine mixture was associated with lower cumulative postoperative opioid consumption and lower early postoperative pain scores than ropivacaine.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"642610"},"PeriodicalIF":6.1,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179933","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 Anterior Quadratus Lumborum Block at the Lateral Supra-Arcuate Ligament Combined with Esketamine on the Quality of Postoperative Recovery After Laparoscopic Radical Surgery for Elderly Patients with Colorectal Cancer: A Randomized Controlled Trial.","authors":"Zhen Dai, Ming Yang, Huan Liu, Xiang Gao, Xiaoyu Zhao, Yan Wang, Xiaoqiong Xia","doi":"10.2147/DDDT.S647461","DOIUrl":"10.2147/DDDT.S647461","url":null,"abstract":"<p><strong>Background: </strong>Postoperative pain, opioid exposure and slow recovery remain common concerns in elderly patients undergoing laparoscopic radical resection of colorectal cancer. We assessed whether anterior quadratus lumborum block at the lateral supra-arcuate ligament (QLB-LSAL) combined with low-dose esketamine improves recovery quality.</p><p><strong>Methods: </strong>In this single-centre, randomized, placebo-controlled trial with blinded outcome assessment, 90 patients aged ≥60 years were assigned to QLB-LSAL with a saline infusion (Group Q), esketamine alone (Group E), or QLB-LSAL with esketamine (Group QE). The prespecified primary endpoint was the QoR-40 total score on postoperative day 3. Esketamine 0.2 mg/kg was given intravenously before induction, followed by 0.2 mg/kg/h until 30 min before the end of surgery in Groups E and QE; Group Q received an equal volume of saline. Longitudinal data were analysed with linear mixed-effects models, with Tukey post-hoc testing and Benjamini-Hochberg correction.</p><p><strong>Results: </strong>Eighty-eight patients were analysed (Q=29, E=30, QE=29). On day 3 the QoR-40 total score was higher in Group QE than in Group E (adjusted difference 8.30, 95% CI 4.37-12.23, Tukey P<0.001); the corresponding day-1 difference was 12.07 (95% CI 7.66-16.47, P<0.001). Group QE also showed better comfort and pain scores, lower remifentanil consumption and fewer day-1 pump activations than Group E, and a higher day-1 QoR-40 score than Group Q (P=0.006). Between-group differences in HADS anxiety scores were not significant after adjustment for multiplicity (QE vs Q on day 1, P=0.068). The incidence of adverse events did not differ between groups.</p><p><strong>Conclusion: </strong>In elderly patients undergoing laparoscopic colorectal cancer surgery, QLB-LSAL combined with low-dose esketamine improved the prespecified day-3 recovery endpoint and reduced early postoperative pain and opioid use compared with esketamine alone; any anxiolytic effect was not confirmed after multiplicity adjustment. Trial registration: ChiCTR2400082301.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"647461"},"PeriodicalIF":6.1,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179831","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":"Reconsidering Treatment Effects in Sequential Ranibizumab-Dexamethasone Therapy for Retinal Vein Occlusion [Letter].","authors":"Jing Chen","doi":"10.2147/DDDT.S659722","DOIUrl":"https://doi.org/10.2147/DDDT.S659722","url":null,"abstract":"","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"659722"},"PeriodicalIF":6.1,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179990","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":"Response Surface Methodology-Assisted Development and Validation of a Stability-Indicating HPLC-PDA Method for Quantification of Medroxyprogesterone Acetate in Microcrystals.","authors":"Camelia Dwi Putri Masrijal, Yahdiana Harahap, Delly Ramadon, Surakit Nathisuwan","doi":"10.2147/DDDT.S603254","DOIUrl":"https://doi.org/10.2147/DDDT.S603254","url":null,"abstract":"<p><p>Reliable and stability-indicating analytical methods are required to support the development and quality control of Medroxyprogesterone Acetate (MPA), particularly in emerging solid-state pharmaceutical systems such as microcrystals. In this analytical method development and validation study, a stability-indicating reversed-phase high-performance liquid chromatography method with photodiode array detection (HPLC-PDA) was developed and validated using Response Surface Methodology (RSM) based on a Box-Behnken design for the quantitative determination of MPA in microcrystalline systems. RSM was applied to systematically evaluate the effects and interactions of critical chromatographic parameters, including methanol proportion, acid modifier concentration, and flow rate, enabling simultaneous optimisation of chromatographic responses related to sensitivity, retention behaviour, and peak symmetry. The optimised method demonstrated balanced chromatographic performance and was validated in accordance with the International Council for Harmonisation guideline Q2(R1). The method exhibited excellent linearity over the concentration range of 0.5-100 µg/mL (r = 0.9999), with accuracy ranging from 99.35% to 100.36% and precision expressed as relative standard deviation (%RSD) below 1.56%. The method also demonstrated adequate sensitivity, with limit of detection (LOD) and limit of quantification (LOQ) values of 0.045 µg/mL and 0.137 µg/mL, respectively, confirming its suitability for quantitative analysis. Forced degradation studies demonstrated that MPA was particularly susceptible to alkaline-thermal stress, resulting in the formation of distinguishable degradation-related peaks adjacent to the parent compound peak, supporting the stability-indicating capability of the method. Overall, the developed RSM-assisted HPLC-PDA method is suitable for routine analysis, stability studies, and formulation-oriented pharmaceutical quality control of MPA microcrystals.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"603254"},"PeriodicalIF":6.1,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179996","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":"Methodological Considerations in Interpreting the Hemodynamic and Respiratory Advantages of Remimazolam During Percutaneous Radiofrequency Ablation [Letter].","authors":"Xiaoyu Xu","doi":"10.2147/DDDT.S659605","DOIUrl":"https://doi.org/10.2147/DDDT.S659605","url":null,"abstract":"","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"659605"},"PeriodicalIF":6.1,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165232","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":"Antifibrotics with Cross-Indication Potential: Challenges and Progress Towards a Universal Fibrosis-Modifying Therapy.","authors":"Claudia Gyimah, Timothy Dempsey, Andrew H Limper","doi":"10.2147/DDDT.S566334","DOIUrl":"https://doi.org/10.2147/DDDT.S566334","url":null,"abstract":"<p><p>Organ fibrosis is a chronic, progressive condition that frequently results in organ dysfunction and failure. Despite its high morbidity and mortality, substantial therapeutic gaps persist for fibrosis across all organ systems. The compartmentalization of fibrosis research by organ system has impeded the development of antifibrotic therapies with cross-organ applicability. However, the shared pathobiology of fibrosis involves convergent signaling through the TGF-β/SMAD axis, receptor tyrosine kinase-mediated fibroblast activation, Wnt/β-catenin-driven myofibroblast differentiation, and amplification of oxidative stress. These conserved mechanisms support the emerging concept of fibrotic endotypes and justify the pursuit of cross-indication antifibrotic drug development, specifically for fibrotic processes in lung, liver, kidney and heart. This review examines the cross-indication potential of currently approved antifibrotics (nintedanib, pirfenidone, nerandomilast) and emerging agents by evaluating their mechanisms of action, preclinical and clinical evidence, translational potential in non-pulmonary fibrosis, and insights from recent clinical trials. Recent data from Phase 3 trials underscore the necessity of multi-target rather than single-target strategies. Key barriers to universal antifibrotic therapy, such as target redundancy, gaps in preclinical-to-clinical translation, biological heterogeneity, and suboptimal trial design, are also discussed. We propose that an endotype guided, precision-medicine strategy using multi-omics profiling and cross-organ adaptive trial designs may help bridge this gap and remains the most promising path toward a universal fibrosis-modifying therapy.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"566334"},"PeriodicalIF":6.1,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149172196","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}