Drug Design, Development and Therapy最新文献

{"title":"Development and Validation of an HPLC-MS/MS Method for Determining I-BET151 in Rat Plasma and Its application to Pharmacokinetic Studies.","authors":"Shengnan Wang","doi":"10.2147/DDDT.S540415","DOIUrl":"10.2147/DDDT.S540415","url":null,"abstract":"<p><strong>Propose: </strong>A bromodomain and extra-terminal domain inhibitor (I-BET151) is effective in treating chronic graft-versus-host disease and has been extensively studied in recent years. However, there is limited research on the pharmacokinetics of I-BET151, especially the lack of methods for determining the concentration of I-BET151 in vivo. Therefore, the purpose of this study is to establish an HPLC-MS/MS method for determining the plasma concentration of I-BET151 and use it for pharmacokinetic study in rats.</p><p><strong>Methods: </strong>The chromatographic column is a Poroshell 120EC-C18 column (50 mm × 4.6 mm, 2.7 μm). The mobile phase consists of water containing 20 mmol ammonium acetate and 0.1% formic acid, and methanol containing 0.1% formic acid, with a flow rate of 0.6 mL/min. The extraction of I-BET151 is liquid-liquid extraction, and the extraction solvent is ether:dichloromethane=2:3. The HPLC-MS/MS method was validated based on the guidelines of quantitative methods for biological samples in the Chinese Pharmacopoeia, including specificity, standard curve, lower limit of quantification, residual effects, precision, recovery rate, matrix effects, stability, etc.</p><p><strong>Results: </strong>The results showed that the established method met the requirements of methodological validation standards and could be used for pharmacokinetic studies of I-BET151. The pharmacokinetic results displayed that the half-life of oral and intravenous administration of I-BET151 was 4.3 h and 3.1 h, respectively. The oral bioavailability was about 60%, indicating that I-BET151 had a high oral bioavailability and appropriate half-life, demonstrating good clinical application prospects.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8679-8689"},"PeriodicalIF":5.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12478601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198565","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":"Safety of Remimazolam in Vulnerable Populations.","authors":"Jia-Yi Ge, Bo-Ran Deng, Xiao-Hua Cao, Xing-Jun Liu","doi":"10.2147/DDDT.S536873","DOIUrl":"10.2147/DDDT.S536873","url":null,"abstract":"<p><p>Vulnerable populations require careful consideration in drug selection due to their unique physiological conditions. Remimazolam, an innovative ultra-short-acting benzodiazepine, presents several advantages, including rapid onset, brief duration of action, and high predictability. Despite the extensive literature on remimazolam, few studies have specifically evaluated its safety in vulnerable patient populations. This review offers a comprehensive analysis of the safety profile of remimazolam in vulnerable populations, including cardiovascular diseases, neurological disorders, hepatic and renal dysfunction, respiratory conditions, metabolic disorders, rare diseases, and special groups such as the elderly and pediatric patients. It assesses recovery outcomes, hemodynamic stability, and adverse events such as respiratory depression and delirium. In our view, the prophylactic potential of remimazolam in these aspects may not be inferior to traditional anesthetic drugs (propofol, sevoflurane, etomidate, etc). and shows a trend of surpassing them in some aspects.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8691-8709"},"PeriodicalIF":5.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12478223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198616","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":"6-Hydroxygenistein Ameliorates High Altitude Brain Injury via Activating PI3K/AKT Signaling Pathway Based on Transcriptomic Analysis and Experimental Validation.","authors":"Yu Xin, Gege Wang, Chenyu Yang, Huiping Ma, Linlin Jing","doi":"10.2147/DDDT.S526988","DOIUrl":"10.2147/DDDT.S526988","url":null,"abstract":"<p><strong>Purpose: </strong>Our Prior research has shown that 6-hydroxygenistein (6-OHG) alleviates hypobaric hypoxia induced brain injury (HHBI) achieved by its powerful antioxidant, anti-inflammatory, and anti-apoptotic capabilities, but its mechanism still requires additional investigation. The objective of this study was to uncover the protective mechanism of 6-OHG against HHBI based on transcriptomics analysis and experimental validation.</p><p><strong>Methods: </strong>The gene levels in brain tissue obtained from previous study were accessed via the RNA-Seq technique. DESeq2 R package was used to identify the differentially expressed genes (DEGs). Functional enrichment analysis and molecular docking were investigated utilizing the clusterProfiler R package and Autodock Vina software, respectively. In experimental validation stage, histological analysis was performed using Hematoxylin-Eosin (HE) staining. Oxidative stress, inflammatory, and apoptotic indexes in brain tissue were measured using commercial kits. Western blot was applied for detecting related protein expression.</p><p><strong>Results: </strong>The RNA-Seq analysis revealed 905 differentially expressed genes (DEGs) between the Con and Mod groups, with 239 upregulated and 666 downregulated. Between the 6-OHG and Mod groups, there were 192 DEGs, including 98 upregulated and 94 downregulated genes. Go and KEGG function analyses highlighted the PI3K/AKT signaling pathway as a crucial regulatory mechanism. Western blot analysis showed that HH exposure caused a decrease in the ratios of p-PI3K/PI3K and p-AKT/AKT in the mouse brain, but this effect was reversed by 6-OHG treatment, indicating that 6-OHG activates the PI3K/AKT signaling pathway. Furthermore, LY294002, a selective PI3K inhibitor, effectively blocked this activation and also abolished the protective effects of 6-OHG on histopathological damage, as well as its antioxidant, anti-inflammatory, and anti-apoptotic activities in HHBI mice.</p><p><strong>Conclusion: </strong>6-OHG mitigates HHBI by activating the PI3K/AKT signaling pathway, suggesting its potential therapeutic application for HHBI treatment.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8641-8656"},"PeriodicalIF":5.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184936","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":"Erratum: Molecular Mechanism of <i>Salvia Miltiorrhiza</i> in the Treatment of Colorectal Cancer Based on Network Pharmacology and Molecular Docking Technology [Corrigendum].","authors":"","doi":"10.2147/DDDT.S569332","DOIUrl":"https://doi.org/10.2147/DDDT.S569332","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.2147/DDDT.S443102.].</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8675-8677"},"PeriodicalIF":5.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198629","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":"Oxysophocarpine Inhibits Apoptosis of Lung Epithelial Cells to Alleviate Acute Lung Injury via KIT/PI3K Signaling Pathway.","authors":"Ziyao Qiao, Kaihua Long, Kairu Ding, Xiaoyan Zhang, Xiaoli Gao, Shanrong Han, Na Zheng, Yun Yang, Jingjing Li, Yaqiong Su, Hong Zhang, Ye Li, Wenbing Zhi, Yang Liu","doi":"10.2147/DDDT.S544479","DOIUrl":"10.2147/DDDT.S544479","url":null,"abstract":"<p><strong>Purpose: </strong>Acute lung injury (ALI) is an acute, diffuse, inflammatory lung injury caused by many factors. Oxysophocarpine (OSC), a quinoline alkaloid sourced from traditional Chinese herbs <i>Sophora flavescens</i> and <i>Sophora davidii</i>, possesses anti-inflammatory and antioxidant properties. However, its effects on ALI are still unclear. This study aims to investigate the role and potential mechanisms of OSC for the treatment of ALI.</p><p><strong>Methods: </strong>The levels of TNF-α, IL-6, and IL-1β in bronchoalveolar lavage fluid (BALF) were measured with an enzyme-linked immunosorbent assay (ELISA). Lung tissue changes were examined through hematoxylin and eosin (HE) staining. Lung cell apoptosis was analyzed using the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Flow cytometry was utilized to detect neutrophil aggregation. Further, the network pharmacology and molecular docking was employed to predict the mechanisms. Key pathways and targets of OSC were confirmed using methods like immunohistochemistry (IHC), immunofluorescence (IF), real-time quantitative PCR (RT-qPCR), and Western blotting (WB).</p><p><strong>Results: </strong>In vivo, OSC treatment significantly inhibited diffuse alveolar injury and interstitial edema compared to the LPS-induced model mice, reduced neutrophil infiltration, and lowered lung epithelial cell apoptosis. In vitro, OSC pretreatment enhanced lung epithelial cell viability and decreased LPS-induced apoptosis. Network pharmacology analysis suggested that OSC mainly targeted key proteins in the PI3K/AKT and apoptosis signaling pathways, such as KIT, PIK3CA, and Bcl-2. Molecular docking confirmed that OSC binds strongly to these targets. Further, PCR, WB, IF, and IHC assay demonstrated that OSC pretreatment elevated PI3K, KIT, and Bcl-2 expressions in BEAS-2B lung epithelial cells and lung tissues.</p><p><strong>Conclusion: </strong>OSC reduced inflammatory cytokine production, neutrophil aggregation, and lung epithelial cell apoptosis via regulating the KIT/PI3K signaling pathway.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8657-8674"},"PeriodicalIF":5.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184994","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":"Development of HPLC-MS/MS Method for Simultaneous Detection of Esketamine and Norketamine: Application to Pharmacokinetics Drug Interactions Affected by Dexmedetomidine.","authors":"Wei Zhou, Zhe Guo, Xianghan Zhang, Wenjiong Wang, Zhongfeng Zheng, Xaingjun Qiu","doi":"10.2147/DDDT.S553389","DOIUrl":"10.2147/DDDT.S553389","url":null,"abstract":"<p><strong>Purpose: </strong>Dexmedetomidine (DEX) and esketamine (ESK) are often used together during anesthesia. This study aimed to establish a sensitive and reliable HPLC-MS/MS method for simultaneous quantification of ESK and its active metabolite norketamine (NORK) in beagle dog plasma and to investigate the pharmacokinetic drug-drug interactions (DDIs) between DEX and ESK/NORK.</p><p><strong>Methods: </strong>A simple protein precipitation method using acetonitrile was applied for plasma sample preparation. After chromatographic separation, analytes were detected by HPLC-MS/MS in positive ion mode using multiple reaction monitoring (MRM). The mass transitions were m/z 238.10→125.10 for ESK, m/z 224.10→125.10 for NORK, and m/z 354.20→209.00 for the internal standard (proadifen). Six beagle dogs were intramuscularly administered 1 mg/kg ESK alone in the first period (ESK group). After a washout, the same dogs received intravenous DEX (2 µg/kg) for 7 consecutive days, followed by co-administration of ESK (DEX+ESK group). The pharmacokinetic parameters of ESK and NORK were calculated using DAS software. Independent-sample <i>t</i> test was used to compare the differences of pharmacokinetic parameters between ESK group and DEX+ESK group, and P < 0.05 indicated a statistically significant difference.</p><p><strong>Results: </strong>Both ESK and NORK exhibited good linearity within the concentration range of 1-400 ng/mL, and the methodological validation met the requirements. When ESK was used in combination with DEX, the main pharmacokinetic parameters of ESK and NORK changed, the C_max, AUC_(0-24) and AUC_(0-∞) of ESK increased, the C_max, of NORK decreased, and the AUC_(0-12) and AUC_(0-∞) of NORK increased too.</p><p><strong>Conclusion: </strong>A novel HPLC-MS/MS method was developed and validated and successfully applied to simultaneously quantify ESK and NORK in beagle dog plasma. The pharmacokinetic DDI results indicate that DEX could inhibit the metabolism of ESK, alter pharmacokinetic characteristics of ESK and its metabolite NORK, and significantly increase the systemic exposure of both ESK and NORK.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8589-8600"},"PeriodicalIF":5.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184956","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 Narrative Review of Phase II and III Clinical Trials for the Pharmacological Treatment of Fibrodysplasia Ossificans Progressiva (FOP): Efficacy, Safety, and Challenges in Treatment Strategies.","authors":"Mohammed S Alharthi","doi":"10.2147/DDDT.S537454","DOIUrl":"10.2147/DDDT.S537454","url":null,"abstract":"<p><strong>Background: </strong>Fibrodysplasia Ossificans Progressiva (FOP) is a rare genetic disorder marked by progressive heterotopic ossification (HO), causing severe disability and reduced life expectancy. Despite advancements in understanding its pathophysiology, effective treatments remain limited. Promising pharmacological approaches include retinoic acid receptor γ (RARγ) agonists, such as palovarotene, and monoclonal antibodies targeting activin A, like garetosmab. However, the rarity of FOP complicates the generation of robust clinical evidence.</p><p><strong>Methods: </strong>This narrative review analysed data from Phase II and III clinical trials on ClinicalTrials.gov, including completed and terminated interventional studies evaluating pharmacological treatments for FOP. Key trial details were systematically extracted and reviewed, including design, interventions, outcomes, and adverse events.</p><p><strong>Results: </strong>Five trials met the inclusion criteria, focusing on palovarotene and garetosmab. Palovarotene significantly reduced HO progression, particularly during active disease phases or flare-ups. Garetosmab showed potential in preventing new HO lesions and reducing lesion activity. However, both treatments posed safety concerns, including premature epiphyseal fusion in younger patients (palovarotene) and systemic adverse events (garetosmab). Terminated trials revealed logistical and ethical challenges, such as recruitment difficulties, small sample sizes, and limitations of placebo-controlled designs.</p><p><strong>Conclusion: </strong>Pharmacological advances, including palovarotene and garetosmab, show promise in managing FOP. Nevertheless, safety concerns and the complexities of clinical trial implementation highlight the need for innovative approaches to ensure effective and equitable treatments. Future research should prioritise long-term safety, efficacy, and patient-centred outcomes to improve FOP management.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8581-8588"},"PeriodicalIF":5.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185016","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 Postoperative Analgesic Effects of Intravenous versus Perineural Dexamethasone Injection Combined with Ropivacaine in Thoracoscopy-Guided Thoracic Paravertebral Block for Thoracoscopic Radical Lung Cancer Resection: A Prospective Randomized Controlled Trial.","authors":"Ke-Wei Wu, Shu-Yu Deng, Xu-Feng Zhang, Da-Wei Zheng, Li-Hong Hu","doi":"10.2147/DDDT.S532934","DOIUrl":"10.2147/DDDT.S532934","url":null,"abstract":"<p><strong>Background: </strong>As an adjuvant, dexamethasone can enhance the analgesic intensity and prolong the duration of nerve blocks. However, to date, no studies have compared the effectiveness of different administration routes of dexamethasone for thoracoscopy-guided thoracic paravertebral block (TTPB). This prospective randomized controlled study evaluated the postoperative analgesic effects of dexamethasone administered intravenously or perineurally in combination with ropivacaine for TTPB in patients undergoing radical lung cancer resection.</p><p><strong>Methods: </strong>A total of 150 patients were randomly assigned to receive dexamethasone intravenously (Group I, n=75) or perineurally (Group D, n=75). Before wound closure, patients in Group I underwent TTPB with ropivacaine while receiving an intravenous dexamethasone injection, whereas patients in Group D received a perineural mixture of ropivacaine and dexamethasone. The primary outcome was the time to first postoperative rescue analgesia. Secondary outcomes included Visual Analogue Scale (VAS) scores, postoperative 48-hour sufentanil consumption in patient-controlled intravenous analgesia (PCIA), postoperative blood glucose levels, postoperative recovery parameters, and incidence of adverse events.</p><p><strong>Results: </strong>Compared with Group I, Group D showed a significantly longer time to first postoperative rescue analgesia, lower VAS scores at all assessed time points, and reduced postoperative 48-hour sufentanil consumption. Group D also showed a smaller increase in postoperative blood glucose levels, an earlier time to first ambulation and a shorter postoperative hospital stay (all <i>P</i> < 0.05). However, the incidence of postoperative nausea was higher in Group D than in Group I (<i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>In TTPB, perineural dexamethasone administration with ropivacaine provided superior and longer-lasting analgesia compared with intravenous administration. Additionally, it accelerated postoperative recovery and shortened hospital stay.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8601-8611"},"PeriodicalIF":5.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184949","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":"Integrative Metabolomics and Ionomics Identify Organ-Specific Responses Associated with Cisplatin Treatment in Mice.","authors":"Rong Sun, Qin Xiao, Houlong Long, Ruili Dang, Shiyuan Zhao, Jinxiu Guo, Xue Chu, Haosen Sun, Yazhou Zhang, Pei Jiang","doi":"10.2147/DDDT.S531720","DOIUrl":"10.2147/DDDT.S531720","url":null,"abstract":"<p><strong>Background: </strong>Cisplatin is a widely used chemotherapeutic agent effective against various malignant tumors. However, its clinical application is limited by severe toxic side effects on multiple vital organs. Understanding the systemic metabolic and elemental alterations associated with cisplatin is essential for developing strategies to mitigate its toxicity.</p><p><strong>Methods: </strong>An integrative metabolomics and ionomics approach was employed to investigate organ-specific responses to cisplatin treatment in mice. Gas chromatography-mass spectrometry (GC-MS) and inductively coupled plasma-mass spectrometry (ICP-MS) were used to analyze metabolic and elemental changes in multiple organs, including the heart, liver, spleen, lungs, kidneys, cortex, hippocampus, brown adipose tissue, and blood. Histopathological evaluation was also performed to complement biochemical analyses.</p><p><strong>Results: </strong>Multivariate statistical analysis indicated that cisplatin was accompanied by significant changes in the levels of several key metabolites, including amino acids, fatty acids, and tricarboxylic acid cycle intermediates. A total of 9 metabolic pathways were implicated, particularly those involved in amino acid biosynthesis, energy metabolism, and redox regulation. In parallel, notable variations in metal ion concentrations, such as Ag, Na, Ca, Zn, Cu, Mg and Fe, were observed across organs. These changes may be linked to alterations in enzyme activity and antioxidant functions.</p><p><strong>Conclusion: </strong>This study provides a comprehensive overview of metabolic and elemental disturbances in vital organs correlated with cisplatin exposure. The findings suggest that modulation of specific metabolites and trace elements may help reduce cisplatin toxicity. The integrative omics approach offers novel insights into the pathways potentially underlying chemotherapy-induced side effects and highlights possible therapeutic targets.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8613-8639"},"PeriodicalIF":5.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184927","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":"Formulation Strategies for Ezetimibe and Its Combinations: Advancing Biopharmaceutical and Therapeutic Potential.","authors":"Sani Ega Priani, Anis Yohana Chaerunisaa, Gofarana Wilar, Iyan Sopyan","doi":"10.2147/DDDT.S550340","DOIUrl":"10.2147/DDDT.S550340","url":null,"abstract":"<p><p>Ezetimibe is a cholesterol absorption inhibitor widely used in the treatment of dyslipidemia. However, its clinical efficacy is limited by poor aqueous solubility and low oral bioavailability. Therapeutic guidelines on dyslipidemia recommend ezetimibe as an adjunct or alternative to statins, particularly in patients who are intolerant to high-dose statins or have inadequate LDL-C reduction. This review summarizes recent advances in ezetimibe formulations, including single-active and combination systems, and discusses their effects on solubility, pharmacokinetics, and therapeutic outcomes. The analysis is based on literature published within the last decade (2015-2025) from reputable scientific databases. Advanced strategies such as solid-state modification, particle size reduction, and lipid or surfactant-based delivery systems have significantly enhanced drug dissolution. In vivo studies report relative bioavailability improvements of approximately 120 to 800% compared to pure drug suspensions/marketed products, translating into favorable pharmacodynamic profiles. Beyond single-active systems, innovative co-delivery with statins such as simvastatin, atorvastatin, rosuvastatin, and lovastatin has demonstrated added pharmacological synergy and supports the development of fixed-dose combination products. Collectively, these advances provide strong evidence that optimized ezetimibe formulations in single-active or combination systems have strong potential to improve the biopharmaceutical profile and future therapeutic application in dyslipidemia management.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8555-8580"},"PeriodicalIF":5.1,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184988","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}