Pharmacology Research & Perspectives最新文献_第2页

Effect of Interleukin-6 Inhibitors on Rheumatoid Arthritis Pain: Overview of Evidence and Mechanistic Pathways. 白细胞介素-6抑制剂对类风湿关节炎疼痛的影响：证据和机制途径综述。

IF 2.3 4区医学

Pharmacology Research & Perspectives Pub Date : 2026-04-01 DOI: 10.1002/prp2.70219

Andrej Belančić, Seher Sener, Almir Fajkić, Ines Potočnjak, Mirjana Stanić Benić, Marijana Vučković, Yusuf Ziya Sener, Marija Rogoznica Pavlović, Antonio Markotić, Josipa Radić, Mislav Radić

{"title":"Effect of Interleukin-6 Inhibitors on Rheumatoid Arthritis Pain: Overview of Evidence and Mechanistic Pathways.","authors":"Andrej Belančić, Seher Sener, Almir Fajkić, Ines Potočnjak, Mirjana Stanić Benić, Marijana Vučković, Yusuf Ziya Sener, Marija Rogoznica Pavlović, Antonio Markotić, Josipa Radić, Mislav Radić","doi":"10.1002/prp2.70219","DOIUrl":"10.1002/prp2.70219","url":null,"abstract":"Rheumatoid arthritis (RA) is an autoimmune systemic disease in which pain remains a major and often refractory symptom even after clinical remission of the disease. Although historically attributed to joint inflammation, recent evidence reveals a multifactorial pathogenesis of RA pain, involving peripheral sensitization, central sensitization, and neuroimmune crosstalk. In these mechanisms, interleukin-6 (IL-6) plays a central role not only as one of the inflammatory mediators but also as a classic and trans-signaling modulator for pain. This review synthesizes current mechanistic and clinical evidence on IL-6 inhibitors, particularly sarilumab and tocilizumab, concerning their effect on pain in RA. Preclinical studies have already demonstrated that IL-6 enhances the excitability of nociceptors through the upregulation of ion channels in dorsal root ganglia; it also promotes glial activation within the spinal cord; however, chronic pain sustains these processes. Blockade of IL-6 receptor reverses these changes and alleviates mechanical hyperalgesia as well as allodynia in different models of diseases. Clinical trials of IL-6 inhibitors have shown that these compounds provide major pain relief, sometimes better than tumor necrosis factor (TNF) inhibitors, most explicitly for patients with elevated baseline C-reactive protein (CRP) or who do not respond to TNF inhibitors. Differences in their pharmacokinetics, receptor binding, and suppression of CRP may translate into differences in their analgesic profiles. However, it is analyzed that a subset of patients with persistently painful rheumatoid arthritis despite IL-6 inhibition demonstrates the existence of non-inflammatory drivers like nociplastic pain and the inadequacy of conventional indices of disease activity to capture the burden of pain.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 2","pages":"e70219"},"PeriodicalIF":2.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Damnacanthal Suppresses Breast Cancer Cells by Inducing Apoptosis and Cell Cycle Arrest via NF-ĸB Signaling. Damnacanthal通过NF-ĸB信号诱导凋亡和细胞周期阻滞抑制乳腺癌细胞。

IF 2.3 4区医学

Pharmacology Research & Perspectives Pub Date : 2026-04-01 DOI: 10.1002/prp2.70249

Onnichar Jongcharoen, Somrudee Reabroi, Pimtip Sanvarinda, Duangjai Tungmunnithum, Warisara Parichatikanond, Darawan Pinthong

{"title":"Damnacanthal Suppresses Breast Cancer Cells by Inducing Apoptosis and Cell Cycle Arrest via NF-ĸB Signaling.","authors":"Onnichar Jongcharoen, Somrudee Reabroi, Pimtip Sanvarinda, Duangjai Tungmunnithum, Warisara Parichatikanond, Darawan Pinthong","doi":"10.1002/prp2.70249","DOIUrl":"10.1002/prp2.70249","url":null,"abstract":"Breast cancer is the most common cancer diagnosed and the leading cause of death for women worldwide. Noni (Morinda citrifolia L.) contains an anthraquinone called damnacanthal (3-hydroxy-1-methoxy-anthraquinone-2-aldehyde), which is known to inhibit the growth of many types of cancer cells. The purpose of this study is to examine the anticancer effects of damnacanthal on cell proliferation, apoptosis, and cell cycle in breast cancer cells and its underlying signaling pathway, including nuclear factor kappa B (NF-ĸB), epidermal growth factor receptors (EGFR), and PI3K/AKT/PTEN. Damnacanthal reduced cell viability in both normal and triple-negative breast cancer cell lines, MCF-7 and MDA-MB-231, respectively. In MCF-7 cells, damnacanthal induced late apoptosis and increased cell cycle arrest in the G0/G1 and S phase, decreased RELA gene expression, and enhanced TNF-α gene expression. However, it had no effect on the protein expression of PI3K/AKT. Damnacanthal exerted anticancer activity on MCF-7 cell lines via blocking NF-ĸB (subunit p65) expression at mRNA levels in the PI3K/AKT-independent manner. These findings highlight the potential benefits of damnacanthal as a promising NF-ĸB inhibitor for cancer prevention or treatment against breast carcinoma.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 2","pages":"e70249"},"PeriodicalIF":2.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13079435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Improving Population Pharmacokinetic Modelling with Artificial Patients using Generative Artificial Intelligence. 利用生成式人工智能改进人工患者群体药代动力学建模。

IF 2.3 4区医学

Pharmacology Research & Perspectives Pub Date : 2026-04-01 DOI: 10.1002/prp2.70241

Verena Schöning, Felix Hammann

{"title":"Improving Population Pharmacokinetic Modelling with Artificial Patients using Generative Artificial Intelligence.","authors":"Verena Schöning, Felix Hammann","doi":"10.1002/prp2.70241","DOIUrl":"10.1002/prp2.70241","url":null,"abstract":"In population pharmacokinetics (PopPK), non-linear mixed effects (NLME) models are used to simultaneously describe a drug's pharmacokinetics (PK) and dynamics (PD) in a patient population using systems of ordinary differential equations. In this field, machine learning is mainly used for data preparation, hypothesis generation, predictive modeling, and model validation. Some approaches to integrate artificially generated information have already been explored, but real-world application is still limited. We therefore conducted a proof-of-concept study to analyze the ability of generative artificial intelligence (AI) to create artificial patient profiles to augment PopPK data sets and assess their influence on parameter estimates. We defined the pharmacokinetic parameters of a hypothetical drug and simulated the concentration curves of 20 patients. We then trained Wasserstein Generative Adversarial Networks (WGANs) with gradient penalty (GP) to generate artificial patients. The data distribution of original and artificial patients was statistically indistinguishable as shown by the Maximum Mean Discrepancy test. Therefore, the WGAN-GP is neither overfitted, that is producing only single instances of artificial patients, nor underfitted, that is producing unrealistic artificial patients. We then combined different shares of original and artificial patients in separate data sets to build and compare PopPK model estimates. Addition of artificial patients led to narrower confidence intervals, indicating more robust parameter estimates, and accentuated the allometric effect of weight on the volume of distribution. In conclusion, we provide a proof-of-concept that generative AI can be used to augment pharmacokinetic data sets, with preliminary evidence suggesting improved parameter estimation.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 2","pages":"e70241"},"PeriodicalIF":2.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13052321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147609589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinical-Pharmacological Drug Information Center of Hannover Medical School: Update From a Tertiary Care University Hospital (2022-2024). 汉诺威医学院临床药理学药物信息中心：来自三级保健大学医院的更新（2022-2024）。

IF 2.3 4区医学

Pharmacology Research & Perspectives Pub Date : 2026-04-01 DOI: 10.1002/prp2.70247

Johannes Heck, Dirk O Stichtenoth, Christoph Schröder, Ruxandra Sabau, Anna-Leena K Heim, Felix Koop, Thorben Pape, Sebastian Schröder, Martin Schulze Westhoff, Benjamin Krichevsky, Martin Klietz, Stephan Greten, Carsten Schumacher

{"title":"Clinical-Pharmacological Drug Information Center of Hannover Medical School: Update From a Tertiary Care University Hospital (2022-2024).","authors":"Johannes Heck, Dirk O Stichtenoth, Christoph Schröder, Ruxandra Sabau, Anna-Leena K Heim, Felix Koop, Thorben Pape, Sebastian Schröder, Martin Schulze Westhoff, Benjamin Krichevsky, Martin Klietz, Stephan Greten, Carsten Schumacher","doi":"10.1002/prp2.70247","DOIUrl":"10.1002/prp2.70247","url":null,"abstract":"Drug information centers (DICs) are institutions dedicated to providing independent and up-to-date information on medications and their usage to healthcare professionals. Here, we provide an update from the clinical-pharmacological DIC of Hannover Medical School, covering the period from April 2022 to December 2024. In total, 438 queries were evaluated. Potential differences between patient-specific and general queries were analyzed with Pearson's chi-squared test or Fisher's exact test. The Holm-Bonferroni method was applied to counteract the problem of multiple comparisons. A curated selection of ten clinically interesting and educational queries is presented and discussed. 85.2% of the queries were patient-specific, and 95.7% were submitted by physicians, predominantly internists, psychiatrists, and surgeons. Indications/contraindications, adverse drug reactions, and pharmacodynamic interactions (PDIs) represented the three most frequent query categories. Compared to our previous research, we observed increases in queries about pharmacotherapy in advanced age and drug use during pregnancy or breastfeeding. As compared to general queries, patient-specific queries were significantly more often related to indications/contraindications (26.2% vs. 49.6%; p < 0.001) and PDIs (24.6% vs. 44.5%, p = 0.003) after adjusting for multiple comparisons. The query characteristics remained relatively stable between our previous investigation and the current analysis (2022-2024), in particular with respect to type of queries, profession of inquiring healthcare professionals, medical specialties of inquirers, and query categories. Changes mainly pertained to higher proportions of queries about pharmacotherapy in advanced age and drug use during pregnancy or breastfeeding.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 2","pages":"e70247"},"PeriodicalIF":2.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13061747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Clinically Relevant Drug Interaction Between Busulfan and Rifampin in the Setting of Hematopoietic Stem Cell Transplant Conditioning. 布苏凡与利福平在造血干细胞移植条件下的临床相关药物相互作用。

IF 2.3 4区医学

Pharmacology Research & Perspectives Pub Date : 2026-04-01 DOI: 10.1002/prp2.70230

Colleen Drangines, Janet Laquet, Ranju Kunwor

{"title":"A Clinically Relevant Drug Interaction Between Busulfan and Rifampin in the Setting of Hematopoietic Stem Cell Transplant Conditioning.","authors":"Colleen Drangines, Janet Laquet, Ranju Kunwor","doi":"10.1002/prp2.70230","DOIUrl":"10.1002/prp2.70230","url":null,"abstract":"Busulfan is an alkylating agent used in combination with other chemotherapeutic agents and has become a common component of conditioning regimens prior to hematopoietic stem cell transplantation. Busulfan has a very narrow therapeutic index corresponding to the area under the plasma concentration-time curve, with supra-therapeutic busulfan levels associated with hepatic and neurologic toxicity and increased transplant-related mortality, while sub-therapeutic levels can be ineffective, resulting in disease relapse or graft failure. Busulfan is believed to be metabolized in the liver via conjugation with glutathione as well as cytochrome P450 isoenzymes. Interactions with medications known to affect CYP3A4, including phenytoin and metronidazole, have been described in multiple instances. This case discusses a drug-drug interaction between busulfan and rifampin, a known CYP3A4 inducer that has limited evidence currently in the literature. Busulfan therapeutic drug monitoring revealed accelerated busulfan clearance determined to be due to rifampin's effect on busulfan metabolism.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 2","pages":"e70230"},"PeriodicalIF":2.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147459243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pharmacological Separation of Mechanosensory Mechanisms in Rat Urinary Bladder Ex Vivo. 体外大鼠膀胱机械感觉机制的药理分离。

IF 2.3 4区医学

Pharmacology Research & Perspectives Pub Date : 2026-04-01 DOI: 10.1002/prp2.70242

Igor B Philyppov, Ganna V Sotkis, Semen I Yelyashov, Valeri G Naidenov, Yaroslav M Shuba

{"title":"Pharmacological Separation of Mechanosensory Mechanisms in Rat Urinary Bladder Ex Vivo.","authors":"Igor B Philyppov, Ganna V Sotkis, Semen I Yelyashov, Valeri G Naidenov, Yaroslav M Shuba","doi":"10.1002/prp2.70242","DOIUrl":"10.1002/prp2.70242","url":null,"abstract":"The local response of the bladder wall to stretch is believed to result from the coordinated activation of mechanosensitive ion channels located in the plasma membrane of the cells that form the wall's urothelial and detrusor smooth muscle (DSM) layers. While the neuronal bladder control is well defined, the data on the mechanisms of local mechanical sensitivity of the bladder wall are either insufficient or contradictory. The involvement of mechanosensitive ion channels, TREK1, TRPV4, and PIEZO1, in determining stretch-dependent properties of the rat bladder wall was assessed by tensiometric measurements of stress-strain dependencies of mucosa-intact and mucosa-devoid DSM strips combined with channel-specific pharmacology. Here we show that TREK1, TRPV4, and PIEZO1 are functionally expressed in the rat bladder DSM and urothelium. TREK1 is coupled with bladder wall relaxation via decreasing DSM excitability and releasing of relaxant mediator(s) from the urothelium. TRPV4 in DSM is involved in gradually developing DSM tone during TREK1-dependent relaxation. Urothelial TRPV4 plays a role in the urothelium-mediated conversion of mechanical stretch into non-voiding spontaneous DSM contractions. DSM-localized PIEZO1 exhibits a higher sensitivity to stretching than TRPV4. Activation of urothelial PIEZO1 leads to the release of the mediator(s) with contractile action on DSM to limit the extent of bladder distention during filling. Our data distinguish the functional involvement of TREK1, TRPV4, and PIEZO1 in the autonomous mechanosensory properties of decentralized urinary bladder wall and provide a strategy for specific pharmacological targeting of bladder contraction/relaxation during different phases of bladder function.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 2","pages":"e70242"},"PeriodicalIF":2.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13042623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147593819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Effects of SGLT2 Inhibitors on Muscle Health in Older Adults: A Systematic Review and Meta-Analysis. SGLT2抑制剂对老年人肌肉健康的影响：系统回顾和荟萃分析

IF 2.3 4区医学

Pharmacology Research & Perspectives Pub Date : 2026-04-01 DOI: 10.1002/prp2.70232

Weena Joongpan, Nittaya Boonmuen, Pimthong Sinchai, Sarawut Lapmanee, Natawat Klamsakul, Nutthapoom Pathomthongtaweechai

{"title":"The Effects of SGLT2 Inhibitors on Muscle Health in Older Adults: A Systematic Review and Meta-Analysis.","authors":"Weena Joongpan, Nittaya Boonmuen, Pimthong Sinchai, Sarawut Lapmanee, Natawat Klamsakul, Nutthapoom Pathomthongtaweechai","doi":"10.1002/prp2.70232","DOIUrl":"10.1002/prp2.70232","url":null,"abstract":"Type 2 diabetes mellitus (T2DM) and obesity are growing global health concerns, particularly in older adults who are at higher risk of sarcopenia. While sodium-glucose cotransporter 2 (SGLT2) inhibitors show promise for glycemic control and weight loss, their effects on muscle health remain unclear. We examined the effects of SGLT2 inhibitors on body weight, fat mass, and muscle mass in T2DM patients. We systematically searched the PubMed, Embase, Scopus, and Cochrane databases for relevant randomized controlled trials (RCTs). Three reviewers screened the studies, and two extracted data and assessed their quality. R software was used to evaluate heterogeneity via Cochran's Q and I2 statistics. Eight RCTs (n = 541) were included. SGLT2 inhibitors significantly reduced body weight (standardized mean difference (SMD) = -0.85, p < 0.001; I2 = 0%) and fat mass (SMD = -0.53, p < 0.001; I2 = 51.1%). A small reduction in muscle mass was observed (SMD = -0.35, p < 0.001; I2 = 22.9%), though substantially smaller than fat loss. Subgroup analysis confirmed that fat mass was reduced with dapagliflozin/ipragliflozin (SMD = -0.67, p < 0.001; I2 = 26.4%) and empagliflozin (SMD = -0.53, p < 0.001; I2 = 66.4%). SGLT2 inhibitors effectively reduce body weight primarily through fat loss in older adults. Although muscle mass declined modestly, the predominance of fat loss suggests weight reduction occurs through favorable metabolic changes. Given the slight muscle mass changes and study heterogeneity, careful monitoring in older adults is warranted, and further studies in diverse populations are needed.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 2","pages":"e70232"},"PeriodicalIF":2.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147434498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Estimation of the Orexin Receptor Occupancy From Human Plasma Pharmacokinetics of Vornorexant, a Novel Dual Orexin 1/2 Receptor Antagonist for the Treatment of Insomnia. 从治疗失眠症的新型双Orexin 1/2受体拮抗剂Vornorexant的血浆药代动力学角度估计Orexin受体占用。

IF 2.3 4区医学

Pharmacology Research & Perspectives Pub Date : 2026-02-01 DOI: 10.1002/prp2.70217

Shunsuke Kamigaso, Yoshihiro Konno, Hirohiko Hikichi, Daiji Kambe, Yoko Mano, Yuichi Tokumaru, Haruyuki Mori, Hironori Yamasaki, Yukihiro Chino, Kenji Hachiuma, Akiko Mizuno-Yasuhira

{"title":"Estimation of the Orexin Receptor Occupancy From Human Plasma Pharmacokinetics of Vornorexant, a Novel Dual Orexin 1/2 Receptor Antagonist for the Treatment of Insomnia.","authors":"Shunsuke Kamigaso, Yoshihiro Konno, Hirohiko Hikichi, Daiji Kambe, Yoko Mano, Yuichi Tokumaru, Haruyuki Mori, Hironori Yamasaki, Yukihiro Chino, Kenji Hachiuma, Akiko Mizuno-Yasuhira","doi":"10.1002/prp2.70217","DOIUrl":"10.1002/prp2.70217","url":null,"abstract":"Vornorexant is a novel dual orexin receptor antagonist (DORA) for the treatment of insomnia with a short elimination half-life. Estimation of the human orexin receptor occupancy can provide insight into the duration of the sleep-promoting effect of DORAs. Herein, we developed a pharmacokinetic-receptor occupancy (PK/RO) model for OX1 and OX2 receptors in rats and estimated their receptor occupancy in humans based on the human plasma concentrations after oral administration of vornorexant. The estimated occupancy of the human OX2 receptor, which is primarily involved in sleep induction, exceeded 70% at 30 min after dosing of therapeutic doses of 5 and 10 mg. The human OX2 receptor occupancy at 6 h post-dose of 5 and 10 mg was estimated to be approximately 50% and 60%, respectively, comparable to the occupancy necessary to exert sleep-promoting effects in rats. Occupancy of the human OX1 receptor by vornorexant was higher than that of the OX2 receptor. The estimated human OX1 and OX2 receptor occupancy decreased with short half-lives depending on the plasma concentration. These results suggest that vornorexant exerts rapid sleep-promoting effects and maintains sleep for at least 6 h, and these estimations of the OX2 receptor occupancy could support the clinical results. Vornorexant may have a favorable PK/RO profile for rapid sleep onset and sufficient sleep maintenance with minimal next-day residual effects in humans.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 1","pages":"e70217"},"PeriodicalIF":2.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12862099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effect of Spinacia oleracea on In Vitro Disintegration and Dissolution of Clopidogrel Bisulfate Tablets. 马齿苋对硫酸氯吡格雷片体外崩解度的影响。

IF 2.3 4区医学

Pharmacology Research & Perspectives Pub Date : 2026-02-01 DOI: 10.1002/prp2.70223

Dana Sadaqa, Hani A Naseef, Asma Radwan, Abdullah K Rabba, Ramzi H M Muqedi

{"title":"Effect of Spinacia oleracea on In Vitro Disintegration and Dissolution of Clopidogrel Bisulfate Tablets.","authors":"Dana Sadaqa, Hani A Naseef, Asma Radwan, Abdullah K Rabba, Ramzi H M Muqedi","doi":"10.1002/prp2.70223","DOIUrl":"10.1002/prp2.70223","url":null,"abstract":"Drug-food interactions may compromise therapeutic efficacy, particularly for life-saving medications such as anticoagulants. Changes in gastric fluid properties, including pH modification and surface film formation, can alter drug dissolution and release. This study evaluated a potential interaction between clopidogrel and spinach and explored the underlying mechanisms. In vitro disintegration and dissolution studies were conducted using HCl and phosphate buffers with and without 5% and 7.5% spinach extract. Drug release was quantified by high-performance liquid chromatography (HPLC), with six media conditions analyzed in triplicate. Disintegration testing was performed in simulated gastric and intestinal fluids and in the presence of spinach leaves to assess the effect of film formation on tablet wetting and disintegration. In vitro-in vivo extrapolation (IVIVE) was assessed using GastroPlus software. Clopidogrel dissolution decreased with increasing spinach concentration in both media. In HCl buffer, dissolution declined from 99% to 94% and 89%, while in phosphate buffer it decreased from 71% to 66% and 56%. These effects were associated with increased pH (HCl: 1.91, 2.83, 2.98; phosphate: 6.81, 8.83, 6.84), increased solution viscosity, 17.63 to 17.67 and 17.70 in HCl buffer, and from 17.44 to 17.50 and 17.54 in phosphate buffer. Moreover, reduced fluid penetration was due to spinach leaves coverage. IVIVE analysis showed weak correlations (R2 = 0.74 in HCl and 0.69 in phosphate buffer). Spinach reduced clopidogrel dissolution in vitro, with statistically significant effects at 5% spinach in HCl buffer (ANOVA test, p-value 0.019) and 7.5% in phosphate buffer (ANOVA test, p-value < 0.001). This interaction appears to be mediated by pH alteration, physical film formation, and potentially metal-drug complexation. Confirmation through in vivo studies is warranted.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 1","pages":"e70223"},"PeriodicalIF":2.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12903545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146181656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to "Repurposing the Antidepressant Sertraline: A Systematic Scoping Review of Its Anticancer Mechanisms". 更正“重新利用抗抑郁药舍曲林：对其抗癌机制的系统范围评价”。

IF 2.3 4区医学

Pharmacology Research & Perspectives Pub Date : 2026-02-01 DOI: 10.1002/prp2.70220

引用次数: 0