Drug Design, Development and Therapy最新文献

{"title":"Comparison of Rocuronium and Cisatracurium in Ophthalmic Surgeries in Association with the Incidence of Intraoperative Bradycardia- A Retrospective Study.","authors":"Shao-Chun Wu, Jo-Chi Chin, Kuo-Chuan Hung, Chih-Yi Hsu, Yung-Fong Tsai, Amina M Illias","doi":"10.2147/DDDT.S532985","DOIUrl":"https://doi.org/10.2147/DDDT.S532985","url":null,"abstract":"<p><strong>Purpose: </strong>Serious complications may arise during the onset and management of intraoperative bradycardia. This study aimed to investigate several factors that may reduce the incidence of intraoperative bradycardia in adult patients undergoing general anaesthesia for various ophthalmic procedures.</p><p><strong>Patients and methods: </strong>A total of 947 adult patients who underwent general anaesthesia for different ophthalmic surgeries in 2020 were initially included. Following the exclusion of 104 cases, 843 patients were eligible for analysis. Patients received either cisatracurium with neostigmine (n = 388) or rocuronium with sugammadex (n = 455) as neuromuscular blocking and reversal agents, respectively. Quantitative neuromuscular monitoring was applied in all cases, while depth of anaesthesia was monitored using the bispectral index (BIS) in selected cases. The primary outcome was the incidence of intraoperative bradycardia, defined as a heart rate of fewer than 60 beats per minute.</p><p><strong>Results: </strong>The group receiving rocuronium and sugammadex demonstrated a significantly lower incidence of intraoperative bradycardia (p < 0.001). This reduction was further supported by logistic regression analysis, both in univariate (OR, 0.07; 95% CI, 0.02-0.24; p = 0.001) and multivariate models (OR, 0.08; 95% CI, 0.02-0.94; p = 0.001). Additionally, this group exhibited a significantly higher rate of BIS monitoring during surgery, alongside a significant reduction in total opioid (p = 0.039) and sevoflurane consumption (p < 0.001).</p><p><strong>Conclusion: </strong>The use of rocuronium is associated with a significant reduction in the incidence of intraoperative bradycardia in adult patients undergoing ophthalmic surgery under general anaesthesia.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7247-7257"},"PeriodicalIF":5.1,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12375305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946457","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":"Irisin's Dual Role in Malignant Tumors and Its Potential as a Biomarker and Therapeutic Target.","authors":"Liqun Mo, Xu Zeng, Yu Liu, Jin Zhang, Li Liu, Yingying Zhang, Yiping Bai","doi":"10.2147/DDDT.S532658","DOIUrl":"https://doi.org/10.2147/DDDT.S532658","url":null,"abstract":"<p><p>Irisin, a myokine secreted by skeletal muscle, has garnered significant attention for its multifaceted physiological roles and emerging potential as both a biomarker and therapeutic target in oncology. This review consolidates current understanding of irisin's impact across various malignancies, focusing on its complex regulation of tumorigenesis through interactions with key signaling pathways including PI3K/AKT, AMPK-mTOR, and STAT3/Snail. Critically, irisin exhibits a paradoxical dual role: it suppresses proliferation, migration, and invasion in cancers such as lung, breast, and pancreatic carcinoma, yet paradoxically promotes the progression of hepatocellular carcinoma. This tissue-specific dichotomy presents a significant therapeutic challenge. Furthermore, inconsistent findings regarding irisin expression levels even within the same tumor type highlight the urgent need for further mechanistic investigation. Future research must prioritize elucidating the context-dependent mechanisms of irisin within the tumor microenvironment and rigorously evaluating its clinical utility as a biomarker through large-scale trials. Resolving these contradictions is essential for developing a unified understanding of irisin's role in cancer biology. Such insights hold promise for paving the way toward novel therapeutic strategies, potentially enhancing the efficacy of personalized cancer therapy.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7185-7205"},"PeriodicalIF":5.1,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12375306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946769","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":"Optimal Programmed Intermittent Epidural Bolus Interval for Video-Assisted Thoracic Surgery Lobectomy: A Biased-Coin Up-Down Study of Ropivacaine-Sufentanil.","authors":"Chengfei Feng, Jijin Wen, Guozhong Lai, Xiaofan Lu, Guanli Luo, Yali Lu, Wei Li, Renchun Lai","doi":"10.2147/DDDT.S538163","DOIUrl":"10.2147/DDDT.S538163","url":null,"abstract":"<p><strong>Purpose: </strong>Programmed intermittent epidural bolus (PIEB) is a novel epidural anesthesia technique for video-assisted thoracic surgery (VATS). However, the optimal setting of the PIEB parameters remains to be determined. This study aimed to determine the optimal time interval for the PIEB regimen of 10 mL ropivacaine 0.15% with sufentanil 0.4 μg/mL within 24 hours of VATS lobectomy.</p><p><strong>Patients and methods: </strong>We conducted a double-blind, sequential allocation trial with a biased-coin up-down design. 42 patients scheduled for VATS lobectomy were enrolled in the study. All participants received a fixed programmed bolus dose of 10 mL of 0.15% ropivacaine combined with 0.4 μg/mL sufentanil. The PIEB interval was initially set at 180 minutes for the first patient and adjusted for subsequent patients according to the biased-coin design, with intervals of 180, 150, 120, and 90 minutes (corresponding to groups 180, 150, 120, and 90, respectively). The primary outcome was the achievement of effective analgesia, defined as the absence of any requirement for patient-controlled epidural analgesia (PCEA) or additional rescue analgesic interventions within 24 hours after the loading dose. Secondary outcomes included the documentation of postoperative adverse effects, such as nausea, vomiting, hypotension, pruritus, and dizziness.</p><p><strong>Results: </strong>A total of 40 patients were included in the study. Using Isotonic Regression analysis, the estimated effective interval for 90% (EI90) of patients was determined to be 97.4 minutes (95% confidence interval [CI]: 91.6-103.1 minutes). The incidence of postoperative hypotension varied significantly across groups, with the highest probability observed in group 90 (64.3%), followed by group 120 (18.8%) and group 150 (11.1%).</p><p><strong>Conclusion: </strong>The estimated effective interval for the EI90 between PIEB of 10 mL of ropivacaine 0.15% with sufentanil 0.4 μg/mL was approximately 100 minutes.</p><p><strong>Trial registration: </strong>Chinese Clinical Trial Registry, ChiCTR2300077174.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7207-7214"},"PeriodicalIF":5.1,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12375332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946763","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":"Traditional Chinese Medicine Monomers and Their Derivatives as a Promising Therapeutic Tool for Hepatocellular Carcinoma by Activation of Mitophagy.","authors":"Jiayu Zhu, Sihan Yin, Shengping Luo, Fei Yu, Kewei Sun","doi":"10.2147/DDDT.S535244","DOIUrl":"https://doi.org/10.2147/DDDT.S535244","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a malignant tumor of the liver. Treatment programs according to its physiological and pathological characteristics have reduced the number of new cases and deaths of HCC, but the morbidity and mortality are still high, posing a significant threat to human health. In recent years, the importance of mitophagy in the treatment of HCC has gradually been recognized. The activation of mitophagy inhibits the survival, proliferation and migration of HCC cells through a variety of pathways, promotes cell apoptosis, and can also reduce drug resistance, providing a new direction for the treatment of HCC. Studies have shown that Traditional Chinese medicine (TCM) monomers and their derivatives can improve the therapeutic efficacy of HCC and slow down disease progression by regulating mitophagy. This article summarizes the potential mechanism of mitophagy in the progression of HCC and comprehensively explores the potential of TCM monomers and their derivatives in the treatment of HCC, providing new perspectives and strategies for clinical treatment.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7069-7087"},"PeriodicalIF":5.1,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946779","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":"Effects of Glycopyrronium Bromide as an Adjuvant Treatment in the Prevention of Nausea and Vomiting After Abdominal, Thyroid, and Breast Surgery: A Multicenter Randomized Controlled Trial.","authors":"Jie Chen, Guangxi Piao, Guohui Luan, Yunming Yu, Wei Zheng, Yue Li, Chao Zhang, Yunzhen Duan, Min Zhao, Yong Zhang, Wei Xiang, Lu Cheng, Chengcheng Ji, Guangyou Duan, He Huang","doi":"10.2147/DDDT.S515670","DOIUrl":"10.2147/DDDT.S515670","url":null,"abstract":"<p><strong>Background: </strong>Effective methods for the prevention of postoperative nausea and vomiting remain to be found. Building upon previous evidence, we examined whether glycopyrrolate bromide had a preventive effect on nausea and vomiting when used as an adjuvant treatment.</p><p><strong>Methods: </strong>In 11 participating hospitals, patients who were scheduled to receive gynecological (n=123), gastrointestinal (n=201), thyroid (n=93), and breast surgery (n=51) under general anesthesia and received postoperative opioids were randomly allocated to receive 4 mg dexamethasone and 4 mg tropisetron (Group C) or 4 mg dexamethasone and 4 mg tropisetron combined with 0.2 mg glycopyrrolate bromide (Group G). The primary outcome of postoperative nausea and vomiting was assessed. The secondary outcomes included the incidences of significant nausea and vomiting (defined based on a rating scale of intensity ≥ 4), vomiting, and extra intervention.</p><p><strong>Results: </strong>In total, 471 patients (234 in Group G and 237 in Group C) were included in the final analysis. The incidence of postoperative nausea and vomiting in Group G was lower than that in Group C (27.8% vs 43.0%, odds rate=0.65, 95% confidence interval =0.50-0.83, <i>P</i>=0.001). Furthermore, the incidences of significant nausea and vomiting (14.1% vs 27.8%, odds rate=0.50, 95% confidence interval=0.35-0.74, <i>P</i><0.001), vomiting (7.3% vs 15.6%, OR=0.46, 95% confidence interval=0.27-0.80, <i>P</i>=0.004) and extra intervention (9.4% vs 17.7%, odds rate=0.53, 95% confidence interval=0.33-0.86, <i>P</i>=0.008) in Group G were all significantly lower than those in Group C. The two groups showed no significant difference in adverse events.</p><p><strong>Conclusion: </strong>The intravenous administration of 0.2 mg glycopyrronium bromide at the end of surgery can be an effective adjuvant treatment strategy for prevention of nausea and vomiting in patients undergoing surgery under general anesthesia and receiving postoperative opioids.</p><p><strong>Trial registration: </strong>The Hospital Ethics Committee of the Second Affiliated Hospital, Chongqing Medical University (Approval ID: 2022-14-1) approved this study. This trial was registered with Identifier NCT05331651 on ClinicalTrials.gov.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7123-7134"},"PeriodicalIF":5.1,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946688","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":"Comparison of Ciprofol Versus Propofol for the General Anaesthesia During Gynecological Day Surgery: A Prospective, Randomized, Double-Blind, Non-Inferiority Trial.","authors":"Shuwen Zhang, Guimin Dong, Xinyuan Shi, Hongyi Xiao, Peihe Nie, Fanceng Ji","doi":"10.2147/DDDT.S539028","DOIUrl":"10.2147/DDDT.S539028","url":null,"abstract":"<p><strong>Purpose: </strong>To compare the safety and efficacy of ciprofol and propofol in general anesthesia for gynecological day surgery.</p><p><strong>Patients and methods: </strong>A total of 196 patients undergoing gynecological day surgery under general anesthesia were randomly divided into ciprofol and propofol group. All patients received total intravenous anesthesia. Anesthesia induction in the ciprofol group: ciprofol 0.5 mg/kg was given intravenously within 1 minute, alfentanil 20 μg/kg was given intravenously within 30 seconds, mivacurium 0.2 mg/kg was given intravenously within 30 seconds, and anesthesia maintenance: ciprofol 1.25 mg/kg/h combined with alfentanil 40 μg/kg/h was given intravenously. Anesthesia induction in the propofol group, propofol 2 mg/kg was administered intravenously within 1 min, alfentanil 20μg/kg was given intravenously within 30s, mivacurium 0.2 mg/kg was administered intravenously within 30s, and anesthesia maintenance: propofol 5 mg/kg/h combined with alfentanil 40 μg/kg/h was administered intravenously. The primary outcome was the success rate of anesthesia (defined as the number of additional study drugs administered ≤ 2 times during anesthesia induction and ≤ 2 times within 10 min during anesthesia maintenance). The secondary outcomes included time to loss of consciousness, hemodynamic changes, depth of anesthesia at different time points, additional narcotic drugs during anesthesia, use of vasoactive agents, awakening time, and incidence of adverse reactions.</p><p><strong>Results: </strong>The success rate of anesthesia in both groups was 100%. There was no difference in the time of consciousness disappearance between the two groups during induction (81.95 vs 79.54s). Compared with the propofol group, the hemodynamics in the ciprofol group were more stable, the depth of anesthesia was better, the number of additional medications was significantly reduced, and the incidence of postoperative adverse reactions was significantly reduced. However, the awakening time of the ciprofol group was significantly longer than that of the propofol group (7.57 vs 5.52 min).</p><p><strong>Conclusion: </strong>Ciprofol demonstrated non-inferior efficacy to propofol for gynecological day surgery anesthesia, while offering superior hemodynamic stability and reduced adverse effects.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7151-7159"},"PeriodicalIF":5.1,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946812","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":"Effects of Different Application Routes of Ozone on Testicular Tissue in Rats with Spinal Cord Ischemia and Reperfusion Injury.","authors":"Ayşegül Küçük, Zeynep Köksal, Süleyman Yeşil, Necmiye Şengel, Şaban Cem Sezen, Işın Güneş, Muharrem Atlı, Gülay Kip, Seda Gökgöz Acar, Abdullah Özer, Mustafa Kavutçu, Mustafa Arslan","doi":"10.2147/DDDT.S528786","DOIUrl":"https://doi.org/10.2147/DDDT.S528786","url":null,"abstract":"<p><strong>Background: </strong>Spinal cord ischemia-reperfusion injury (IRI) is a serious condition that can develop after spinal and thoracoabdominal surgeries or spinal cord traumas. The aim of this study was to investigate the effects of different administration routes of ozone on testicular tissue in rats with spinal cord ischemia and reperfusion injury.</p><p><strong>Methods: </strong>Rats were divided into five groups (n:5): control (C), ischemia-reperfusion (IR), IR-rectal ozone (IR+RO), IR-intratechal ozone (IR+ITO), and IR-intraperitoneal (i.p) ozone (IR+IPO). Ozone-oxygen mixture was administered 30 minutes before midline laparotomy: 1 mg/kg (50 µg/mL) by rectal insufflation to the IR+RO group, 20 µL (20 µg/mL) intratechally to the IR+ITO group, and 0.7 µg/kg (50 µg/mL) intraperitoneally to the IR+IPO group. The spinal cord IR model was established. The testicular tissue was collected for histopathological and biochemical analyses.</p><p><strong>Results: </strong>The Malondialdehyde (MDA) levels and Paraoxonase-1 (PON1) activities were significantly lower in the IR+RO, IR+ITO, and IR+IPO groups than in the IR group. Catalase (CAT) was significantly higher in the IR+ITO and IR+IPO groups than in the IR group. While the Cosentino score was significantly higher in the IR group than in the C group (p<0.001), it was significantly lower in the IR+RO, IR+ITO and IR+IPO groups than in the IR group (p<0.001, all).</p><p><strong>Conclusion: </strong>Ozone can regulate the negative effects of IRI by regulating cellular oxidative stress mechanisms. This effect can be achieved most effectively on testis tissue in the spinal cord IRI model through intrathecal and intraperitoneal administration.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7089-7098"},"PeriodicalIF":5.1,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946637","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":"Synergistic Mechanisms of Traditional Chinese Medicine and Proteasome Inhibitors in Multiple Myeloma Therapy: A Comprehensive Review.","authors":"Youya Dai, Yongming Zhou, Hailin Chen","doi":"10.2147/DDDT.S531815","DOIUrl":"https://doi.org/10.2147/DDDT.S531815","url":null,"abstract":"<p><strong>Background: </strong>Multiple myeloma (MM) is a clonal plasma cell malignancy characterized by bone marrow infiltration, monoclonal immunoglobulin production, and multisystem damage. Proteasome inhibitors (PIs) such as bortezomib, carfilzomib, and ixazomib have significantly improved progression-free and overall survival in MM patients. However, drug resistance and adverse effects-including peripheral neuropathy and cardiotoxicity-remain major limitations to long-term disease control.</p><p><strong>Objective: </strong>This review aims to comprehensively evaluate the synergistic mechanisms and therapeutic potential of Traditional Chinese Medicine (TCM) in combination with PIs for the treatment of MM, from molecular insights to translational outcomes.</p><p><strong>Methods and scope: </strong>We synthesized findings from preclinical studies, pharmacological investigations, and cohort analyses that examine the interplay between TCM bioactives and PI-based regimens. Focus is given to the modulation of MM-related signaling pathways (eg, NF-κB, STAT3, PI3K/Akt), apoptotic cascades, proteasomal degradation processes, and the bone marrow microenvironment.</p><p><strong>Results: </strong>Evidence suggests that specific TCM compounds-such as curcumin, baicalein, icariin, and berberine-can potentiate PI-induced cytotoxicity, reverse resistance mechanisms, reduce inflammatory damage, and protect against PI-associated toxicities. Several Chinese herbal formulations, including Fuzheng Peiyuan and Huanglian Jiedu decoctions, have demonstrated immunomodulatory and anti-myeloma effects in vivo and in human cohorts. These synergistic actions may enhance the efficacy and tolerability of PIs in MM therapy.</p><p><strong>Conclusion: </strong>Integrating TCM with proteasome inhibitors represents a promising strategy to optimize MM treatment by simultaneously targeting malignant cells and the tumor microenvironment. Further mechanistic research and well-designed clinical trials are warranted to validate and standardize this combinational approach for broader clinical adoption.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7099-7109"},"PeriodicalIF":5.1,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946743","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":"Influencing Factors of Treatment Response to Rituximab in Refractory Membranous Nephropathy.","authors":"Lianzi Ma, Li Yang, Jing Zheng","doi":"10.2147/DDDT.S538971","DOIUrl":"https://doi.org/10.2147/DDDT.S538971","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to identify influencing factors associated with the efficacy of rituximab in treating refractory membranous nephropathy (MN), characterized by persistent proteinuria and unresponsive to conventional immunosuppressive therapies. We sought to determine clinical and biochemical predictors for positive therapeutic outcomes and optimize patient selection criteria.</p><p><strong>Methods: </strong>A total of 160 patients with biopsy-confirmed refractory MN (meeting criteria of eGFR > 30 mL/min/1.73 m², significant proteinuria, positive PLA2R-Ab, and prior treatment failure) were studied. Patients received rituximab (375 mg/m²) with 24-month monitoring. Baseline demographic, clinical, and biochemical data underwent univariate and multivariate logistic regression analyses, while ROC curve analysis evaluated predictive accuracy.</p><p><strong>Results: </strong>Responders (n=113) exhibited higher serum albumin, lower serum creatinine, reduced 24-hour urine protein, higher eGFR, and lower PLA2R-Ab levels (all P < 0.001) versus non-responders (n=47). Multivariate analysis identified these as independent predictors. The combined indices yielded an AUC of 0.99 (with 93.8% sensitivity and 97.9% specificity; P < 0.001), demonstrating excellent accuracy for identifying patients most likely to benefit from rituximab therapy.</p><p><strong>Conclusion: </strong>Rituximab demonstrates efficacy in treating refractory MN, with specific clinical and biochemical markers providing significant predictors of treatment success. The biomarker combination (serum albumin, creatinine, 24-hour urine protein, eGFR, PLA2R-Ab) offers exceptional predictive accuracy for treatment outcomes, providing clinicians with a practical tool to guide personalized treatment decisions and optimize resource allocation in refractory MN management.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7059-7067"},"PeriodicalIF":5.1,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946775","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":"Bioequivalence Study of Palbociclib Tablets in Healthy Volunteers.","authors":"Yiting Hu, Na Zhao, Haojing Song, Jian Zhang, Lusha Bi, Bo Qiu, Yufang Xu, Caiyun Jia, Wanjun Bai","doi":"10.2147/DDDT.S518617","DOIUrl":"10.2147/DDDT.S518617","url":null,"abstract":"<p><strong>Objective: </strong>Bioequivalence of palbociclib tablets was evaluated in healthy volunteers under fasting and fed conditions in this study.</p><p><strong>Methods: </strong>This bioequivalence trial, which randomized subjects to receive palbociclib under fed or fasted conditions, generated these results. High-performance liquid chromatography-mass spectrometry (HPLC-MS) was employed to determine palbociclib concentrations in plasma from collected blood samples. Pharmacokinetic (PK) parameters were calculated using the non-compartmental analysis (NCA) module within Phoenix WinNonlin version 8.2. Statistical analysis of key pharmacokinetic parameters-maximum plasma concentration (C_max), area under the concentration-time curve from zero to last quantifiable time (AUC_0-t), and area under the curve from zero to infinity (AUC_0-∞)-was conducted using the bioequivalence (BE) module within WinNonLin. A total of 68 healthy subjects were enrolled and randomized to either a fasted or a fed group. All subjects were randomized into T-R and R-T sequences (T: test formulation; R: reference formulation).</p><p><strong>Results: </strong>The geometric mean ratios (T/R) of C_max, AUC_0-t and AUC_0-∞ of palbociclib in plasma were 97.96%, 96.16%, and 96.02% under fasting conditions; The geometric mean ratios (T/R) of C_max, AUC_0-t and AUC_0-∞ of palbociclib in plasma were 95.47%, 96.49%, and 96.36% under fed conditions. All 90% confidence intervals for the geometric mean ratios were contained entirely within the range of 80.00% to 125.00%. Under the fasted and fed conditions, the test preparation and the reference preparation of palbociclib tablets were bioequivalent. Adverse events (AEs) occurred at similar rates in the fasted and fed groups.</p><p><strong>Conclusion: </strong>The result indicated that the test preparation and the reference preparation of palbociclib tablets were bioequivalent under the fasted and fed conditions. The safety of the two preparations was good.</p><p><strong>Clinical trial registration: </strong>This trial was registered on the Chinese Clinical Trial website (http://www.chinadrugtrials.org.cn/index.html # CTR20220977).</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7111-7121"},"PeriodicalIF":5.1,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946799","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}