Drug Design, Development and Therapy最新文献

{"title":"Effects of Prophylactic Infusion of Equivalent Doses of Norepinephrine and Phenylephrine in Preventing Spinal Anesthesia-Induced Hypotension During Cesarean Delivery on Fetal and Maternal Outcomes: A Dual-Center, Non-Inferiority Controlled Trial [Retraction].","authors":"","doi":"10.2147/DDDT.S563756","DOIUrl":"https://doi.org/10.2147/DDDT.S563756","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.2147/DDDT.S514091.].</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8049-8050"},"PeriodicalIF":5.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069339","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":"Intravenous Anesthesia with Ciprofol and Remimazolam Besylate for Painless Gastroscopy: A Prospective, Single-Center, Randomized Controlled Trial.","authors":"Lin Li, Yusi Zhu, Jie Zhu, Mingyue Zeng, Yu Duan, Pengfei Cheng, Xiang Zhou","doi":"10.2147/DDDT.S534842","DOIUrl":"10.2147/DDDT.S534842","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate whether combining ciprofol and remimazolam offers superior safety and efficacy compared to propofol or ciprofol monotherapy for sedation during painless gastroscopy. We hypothesize improved hemodynamic and respiratory stability with the combination.</p><p><strong>Methods: </strong>A total of 641 patients undergoing gastroscopy were randomly assigned to one of three groups. Group P (Propofol) received an intravenous bolus of propofol at a dose of 1.5 mg/kg. Group CR (Ciprofol + Remimazolam) received an initial intravenous dose of remimazolam (0.08 mg/kg), followed by ciprofol (0.25 mg/kg). Group C (Ciprofol) received an intravenous bolus of ciprofol at a dose of 0.4 mg/kg. Sedation depth was maintained within the target range (Bispectral Index 40-60) through the administration of supplemental doses: propofol (10-20 mg boluses) in Group P, and ciprofol (2.5-5 mg boluses) in Groups CR and C.</p><p><strong>Results: </strong>Compared with group P, groups CR and C demonstrated significantly lower incidences of hypotension (CR: 7.8% vs P: 21.6%; C: 12.3% vs P: 21.6%; all <i>P</i> values < 0.001), mild hypoxia (CR: 8.8% vs P: 18.1%, <i>P</i> = 0.005; C: 7.7% vs P: 18.1%, <i>P</i>=0.001), and severe hypoxia (CR: 4.6% vs P: 9.8%, <i>P</i> = 0.038; C: 4.1% vs P: 9.8%, <i>P</i> = 0.020). Group C exhibited significantly longer induction time (1.62 ± 0.66 min, <i>P</i> < 0.001), recovery time (13.73 ± 3.82 min, <i>P</i> < 0.001), and operating room time (23.05 ± 6.38 min, <i>P</i> < 0.001) compared to both other groups. Additionally, gastroenterologist and anesthesiologist satisfaction was significantly higher in group CR than in groups P and C (all <i>P</i> values < 0.001).</p><p><strong>Conclusion: </strong>The combination of ciprofol and remimazolam exerts a lesser impact on the respiration and circulation of patients undergoing gastroscopy, and demonstrates superior safety and efficacy compared to the use of propofol or ciprofol alone.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8083-8095"},"PeriodicalIF":5.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069357","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":"Salidroside Improves Periodontitis by Mitigating Inflammatory Reactions and Enhancing Osteogenic Differentiation of Human Periodontal Ligament Stem Cells.","authors":"Wanheng Li, Qing Liu, Siyu Chen, Mengfan Zhi, Peng Yang, Yuxing Zhang, Zhaoyan Wu, Jun Zhang, Qiang Feng","doi":"10.2147/DDDT.S530311","DOIUrl":"10.2147/DDDT.S530311","url":null,"abstract":"<p><strong>Purpose: </strong>Salidroside (Sal), a significant bioactive compound found in <i>Rhodiola rosea</i>, is documented to possess various pharmacological properties. This study investigated the effects of Sal in alleviating periodontitis.</p><p><strong>Methods: </strong>The rat periodontitis model was utilized to assess the therapeutic impact of Sal on periodontitis. Human periodontal ligament stem cells (hPDLSCs) were used to investigate the effect of Sal on lipopolysaccharide (LPS)-inhibited osteogenic differentiation. RNA sequencing (RNA-seq), and Western blot were employed to analyze the genes and proteins impacted by Sal treatment.</p><p><strong>Results: </strong>Sal significantly alleviated the alveolar bone loss and gingival inflammation in rats periodontitis model. Sal demonstrated a dose-dependent pattern of promoting osteogenesis on hPDLSCs. A concentration of 0.5 μM Sal could effectively counteract the impact of LPS on osteogenic differentiation. Mechanically, Sal inhibited the ratios of phospho-IκBα(p-IκBα)/IκBα and phospho-p65(p-p65)/p65 in Nuclear Factor kappa-B (NF-κB) pathway and reduced the expressions of interleukin-6 (IL-6) and interleukin-8 (IL-8). Sal increased the expression of lymphoid enhancer-binding factor 1 (LEF1).</p><p><strong>Conclusion: </strong>Sal promoted the osteogenic differentiation by inhibiting the activation of the NF-κB pathway and increasing the expression of LEF1.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8097-8114"},"PeriodicalIF":5.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069292","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":"Exploration of Key Genes and Molecular Mechanisms in Mice with Perioperative Neurocognitive Disorders Treated with Remimazolam Based on Transcriptomics and Experimental Verification.","authors":"Shilin Yu, Bo Chen, Mei Zhang, Rong Hu, Jin Luo, Ju Li, Wen Hu, Xiaohua Zou","doi":"10.2147/DDDT.S541958","DOIUrl":"10.2147/DDDT.S541958","url":null,"abstract":"<p><strong>Background: </strong>As the number of elderly patients grew, perioperative neurocognitive disorder (PND) from drug - induced anesthesia and surgery drew more attention. Studies showed remimazolam could reduce PND. Thus, exploring key target genes in remimazolam's intervention of PND was crucial.</p><p><strong>Methods: </strong>In this study, behavioral observations were conducted using the PND model. Hippocampal tissues from 15 mice (5 PND, 5 PND, and 5 intervention groups) were collected for total RNA extraction and mRNA sequencing. Candidate genes were identified via differential expression analysis and intersection. Key genes were determined through overlapping three algorithms in protein-protein interaction (PPI) analysis and expression verification. Functional enrichment, immune infiltration, and molecular docking analyses were performed, with their expression levels further validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR).</p><p><strong>Results: </strong>There were significant differences in the behavior of mice among different groups. Based on the intersection of up-and down-regulated genes in 357 differentially expressed genes1 (DEGs1) and 323 DEGs2, a total of 38 candidate genes were identified. Finally, we selected <i>Jph3</i> and <i>Caly</i> as the key genes for subsequent study. Moreover, the PCR results showed that the expression of key genes in the PNG group was nearly twice that of the control group (p < 0.05). In-depth research revealed that pathways like glutamate receptor binding, tau protein binding, and GABA-gated chloride ion channel activity played important roles in disease occurrence. Meanwhile, 5 immune cells (including dendritic cells, macrophages, and gamma delta T cells) showed substantial differences between the model and PND groups, potentially contributing to disease development. Additionally, only Jph3 was regulated by mmu-miR-6969-5p and mmu-miR-186-5p. Both Jph3 and Caly had good binding abilities with remimazolam (< -5.0 kcal/mol), highlighting their potential as therapeutic agents for PND.</p><p><strong>Conclusion: </strong>This study identified 2 validated key genes (Jph3 and Caly), providing potential therapeutic targets for PND patients.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8115-8133"},"PeriodicalIF":5.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069386","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":"Drug-Drug Interactions and Initial Dosage Optimization of Quetiapine in Patients with Depression: A Real-World Study.","authors":"Xiao Chen, Yue Zhang, Di Yin, Ying-Wei Jin, Su-Mei He, Cun Zhang, Dong-Dong Wang","doi":"10.2147/DDDT.S538856","DOIUrl":"10.2147/DDDT.S538856","url":null,"abstract":"<p><strong>Objective: </strong>Quetiapine has been used for treating patients with depression; however, drug-drug interactions (DDIs) deeply limit its individualized administration. This study explored DDIs and initial dose recommendation of quetiapine in depression patients based on real-world data.</p><p><strong>Methods: </strong>Sixty-four real-world depression patients were used to investigate the effects of drug combinations on quetiapine using a non-linear mixed effect model (NONMEM).</p><p><strong>Results: </strong>In the final model, paroxetine and fluvoxamine were included as covariates, which significantly affected the clearance rate of quetiapine, with ratios of about 1.00:0.54:0.48:0.26 in patients with depression who were not accompanied by paroxetine or fluvoxamine, patients with depression who were accompanied by paroxetine, patients with depression who were accompanied by fluvoxamine, and patients with depression who were accompanied by paroxetine and fluvoxamine. Furthermore, the initial dose optimizations of quetiapine were 20 and 16 mg/kg/day for depression patients not accompanied by paroxetine or fluvoxamine who weighted 40-80, and 80-120 kg, respectively. The initial dose of quetiapine was 8 mg/kg/day for depression patients accompanied by paroxetine who weighted 40-120 kg. The initial dose of quetiapine was 8 mg/kg/day for depression patients accompanied by fluvoxamine, who weighted 40-120 kg. The initial dose optimization of quetiapine was 4 mg/kg/day for depression patients accompanied by paroxetine and fluvoxamine who weighted 40-120 kg.</p><p><strong>Conclusion: </strong>Our study explored DDIs and initial dose recommendation of quetiapine in depression patients from the real world, and the initial dose optimization of quetiapine was recommended based on the interaction with paroxetine or fluvoxamine.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8051-8067"},"PeriodicalIF":5.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063702","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":"Acute Kidney Injury Associated with the Concomitant Use of Vancomycin and Piperacillin-Tazobactam.","authors":"Dayu Chen, Jingjing Kan, Qiaoling Gu, Yi-Chen Li, Yunxing Liu, Mengzhu Kong, Jinchun Liu, Haixia Zhang","doi":"10.2147/DDDT.S524370","DOIUrl":"10.2147/DDDT.S524370","url":null,"abstract":"<p><p>In recent years, the increased use of vancomycin (VAN) in combination with piperacillin-tazobactam (TZP) has raised significant concerns in clinical practice regarding the heightened risk of acute kidney injury (AKI). This topic has become a focal point in clinical therapeutics due to the widespread application of VAN alongside TZP. The specific mechanisms underlying vancomycin and piperacillin-tazobactam (VPT) associated AKI remain unclear. In this review, we discuss several controversial or underexplored aspects of current research. While the majority of literature links VPT to an elevated risk of AKI, numerous studies present conflicting outcomes. Mechanisms proposed for the increased risk of AKI associated with VPT, based on clinical observations and animal studies, include additive toxic effects, increased VAN exposure due to concomitant use with TZP, exacerbated VAN-induced oxidative stress injury in proximal renal tubule by TZP, pseudo-nephrotoxicity mediated by VPT-induced impaired creatinine secretion, or a combination of the aforementioned mechanisms. Additionally, this review outlines potential strategies that might effectively mitigate the risk of VPT-induced AKI, offering insights and future implications in the realm of pharmacovigilance.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7947-7965"},"PeriodicalIF":5.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063736","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":"Establishment and Validation of a UPLC-MS/MS Method for Quantitative Determination of Zanubrutinib and Posaconazole in Rat Plasma: Application in Drug-Drug Interaction Studies.","authors":"Hailun Xia, Yuxin Shen, Xinhao Xu, Jun Wu, Guanyang Lin, Xiaoxiang Du","doi":"10.2147/DDDT.S531381","DOIUrl":"10.2147/DDDT.S531381","url":null,"abstract":"<p><strong>Purpose: </strong>Zanubrutinib, a second-generation Bruton's tyrosine kinase (BTK) inhibitor, has been demonstrated to treat multiple B-cell malignancies, which include Waldenström's macroglobulinemia, chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma and mantle cell lymphoma (MCL). There have been very few studies of drug-drug interactions (DDI) between zanubrutinib and other medications.</p><p><strong>Methods: </strong>The current study validated a sensitive and reliable quantitative detection of zanubrutinib and posaconazole in rat plasma using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The plasma samples were prepared by protein precipitation with the addition of acetonitrile, using orelabrutinib and fluconazole as internal standards (IS). Fifteen male Sprague-Dawley (SD) rats were randomly and equally divided into three groups: posaconazole (40 mg/kg) administered orally alone, zanubrutinib (16 mg/kg) received orally alone, co-administered orally zanubrutinib (16 mg/kg) and posaconazole (40 mg/kg).</p><p><strong>Results: </strong>The methodology was validated, and the precision, stability, accuracy, matrix effect and extraction recovery were within the permissible values. This method was successfully applied to evaluate the potential DDI between zanubrutinib and posaconazole, and the results showed a significant 0.98-fold increase in both AUC_0-t and AUC_0-∞ of zanubrutinib when zanubrutinib was administered concomitantly with posaconazole. In addition, posaconazole significantly increased AUC_0-t, AUC_0-∞, T_max, and C_max of zanubrutinib by 2.31-, 4.78-, 2.93-, and 0.86-fold, respectively, while CL_z/F significantly decreased by 83.5%.</p><p><strong>Conclusion: </strong>These data suggested that when zanubrutinib was co-administered with posaconazole, there are increased exposures to both zanubrutinib and posaconazole. The current results contributed to a better understanding of the metabolism and DDI of zanubrutinib and posaconazole, and it is necessary to further investigate and validate the results in humans.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7967-7977"},"PeriodicalIF":5.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063762","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":"Population Pharmacokinetic and Pharmacodynamic Modeling of Enteric-Coated Aspirin Capsule and Tablet Formulations in Healthy Subjects.","authors":"JaeEun Koh, Juyoung Khwarg, Kyung-Sang Yu, SeungHwan Lee, In-Jin Jang, Soyoung Lee","doi":"10.2147/DDDT.S533428","DOIUrl":"10.2147/DDDT.S533428","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to develop a population pharmacokinetic-pharmacodynamic (PK-PD) model to predict the PKs of acetylsalicylic acid (ASA) and salicylic acid (SA), and their effects on thromboxane B2 (TXB2) inhibition following oral administration of two enteric-coated aspirin formulations.</p><p><strong>Patients and methods: </strong>Data from two Phase I studies in healthy Korean subjects were used to develop the PK-PD model. A nonlinear mixed effect modeling approach was implemented using Monolix^®, based on 669 plasma concentrations of ASA and SA and 83 serum TXB2 concentrations from 44 subjects. Simulx^® was used for model-based simulation and external validation using published literature data. Differences in absorption profiles between two formulations were assessed as a covariate effect.</p><p><strong>Results: </strong>The PK of aspirin was well described by a one-compartment model for ASA and a two-compartment model for SA, incorporating pre-systemic metabolism and dual absorption. A turnover model with an Emax function captured the TXB2 inhibition. The capsule formulation showed faster absorption (0.22 h^-1) than the tablet (0.053 h^-1), but this did not affect TXB2 inhibition. Body weight significantly influenced ASA-to-SA metabolism and SA clearance. External validation confirmed that the model adequately predicted PK and PD profiles at both 80 mg and 160 mg doses, with simulated TXB2 inhibition showing similar responses between formulations at steady state, exceeding 80%.</p><p><strong>Conclusion: </strong>This model adequately described the PK and PD of enteric-coated aspirin and demonstrated comparable TXB2 inhibition between the capsule and tablet formulations, supporting their potential interchangeability in clinical practice.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7853-7863"},"PeriodicalIF":5.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063306","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":"Shatai Heji Mitigates Sjögren Disease-Induced Xerostomia by Regulating AQP5, NF-κB, and p38 MAPK Signaling Pathwaysaff.","authors":"Fangbin Liu, Jiyuan Chen, Chunai Gong, Minyan Chen, Gang Yang, Chun Chen, Ru Yao, Shengnan Li, Rong Wang, Yongfang Yuan","doi":"10.2147/DDDT.S526278","DOIUrl":"10.2147/DDDT.S526278","url":null,"abstract":"<p><strong>Introduction: </strong>Xerostomia, commonly caused by Sjögren disease (SjD) or head and neck radiotherapy, significantly impairs patients' quality of life, yet effective treatments remain limited. Traditional Chinese Medicine (TCM) offers promising alternatives due to its favourable efficacy and low toxicity. Shatai Heji (STHJ), a compound TCM formulation designed to nourish yin and invigorate qi, shows therapeutic potential for xerostomia. This study aimed to establish quality control standards for STHJ and evaluate its pharmacodynamics, safety, and mechanisms of action in models of xerostomia.</p><p><strong>Methods: </strong>A qualitative identification method was developed for the twelve herbal components of STHJ, with quantification of active constituents, focusing on quality markers for Astragalus and Rehmannia. Xerostomia was induced in Sprague-Dawley (SD) rats using a muscarinic receptor antagonist, and in BALB/c mice with SjD. Histological examination of major organs and salivary glands was performed, and aquaporin-5 (AQP5) expression in submandibular glands was assessed via Western blotting and immunohistochemistry. Therapeutic effects were evaluated through salivary secretion, glandular weight, and biochemical markers. In SjD mice, submandibular gland immunofluorescence and ELISA were used to assess inflammatory cytokines (TNF-α, TNF-β, IFN-γ, IL-6) and autoantibodies (anti-SSA/Ro, anti-SSB/La). Western blotting was used to analyse NF-κB and MAPK p38 pathway activation. Acute toxicity was assessed in SD rats.</p><p><strong>Results: </strong>STHJ significantly improved xerostomia symptoms, increased salivary output, upregulated AQP5, and preserved glandular morphology. It reduced fibrosis, suppressed inflammatory cytokine expression, and inhibited immune cell infiltration. Mechanistically, STHJ attenuated activation of NF-κB and MAPK p38 pathways. No acute toxicity was observed.</p><p><strong>Conclusion: </strong>This is the first study to establish quality control standards for STHJ and to demonstrate its anti-inflammatory and immunomodulatory effects in xerostomia models. The findings suggest that STHJ may serve as a safe and effective therapeutic option for xerostomia associated with SjD and other conditions.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7979-7998"},"PeriodicalIF":5.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063381","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":"Compatibility and Physico-Chemical Stability of Six Intravenous Mixtures for Postoperative Multimodal Analgesia.","authors":"Carmen Lopez-Cabezas, Judith Baguena, Mireia Marcé Briansó, Gemma Gotor, Susana Ceamanos, Tomas Cuñat, Francesc Broto-Puig, Dolors Soy","doi":"10.2147/DDDT.S543730","DOIUrl":"10.2147/DDDT.S543730","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the physical-chemical compatibility of six drug combinations used in intravenous multimodal postoperative analgesia under differing storage conditions and different containers.</p><p><strong>Methods: </strong>The analgesic mixtures studied were ternary and quaternary combinations of tramadol and ketamine with dexketoprofen or ketorolac, plus methadone in some mixtures, all diluted in saline solution. Physical compatibility, pH and concentration of drugs (ultra high performance liquid chromatography (UHPLC-DAD)) were determined 48 hours post-preparation (room temperature) and after 30 days (2°-8°C) for the mixtures in polyolefin bags, and after 14 days at room temperature for those mixtures in silicone and polyisoprene elastomers.</p><p><strong>Results: </strong>No physical changes were observed, and pH remained stable throughout the study. For all five drugs in polyolefin bags the recovery percentage remained within the range 95-105%. Regarding mixtures prepared in elastomers, the recovery percentage for tramadol and dexketoprofen stayed within the range 95-105%, while for methadone it was less than 40%. A subsequent extraction with methanol demonstrated the methadone adsorption on the container walls, more pronounced in the silicone than in the polyisoprene reservoirs.</p><p><strong>Conclusion: </strong>Analgesic mixtures of tramadol and ketamine with adjuvants (dexketoprofen or ketorolac, with or without methadone) showed physicochemical stability for 48 hours at room temperature and up to 30 days at 2°-8°C in polyolefin bags. However, the combination of tramadol, dexketoprofen, and methadone was unstable in both tested elastomeric devices due to methadone adsorption, making it unsuitable for clinical use. These findings underscore the critical role of container material in drug stability.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8041-8048"},"PeriodicalIF":5.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063681","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}