Pharmacology Research & Perspectives最新文献

{"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":"<p><p>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.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 1","pages":"e70223"},"PeriodicalIF":2.6,"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}

{"title":"Correction to \"Repurposing the Antidepressant Sertraline: A Systematic Scoping Review of Its Anticancer Mechanisms\".","authors":"","doi":"10.1002/prp2.70220","DOIUrl":"10.1002/prp2.70220","url":null,"abstract":"","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 1","pages":"e70220"},"PeriodicalIF":2.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12865120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146106762","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}

{"title":"Exploring Pembrolizumab-Induced IM3OS in a Patient With Bladder Cancer.","authors":"Ching-Cheng Chan, Ming-Jen Lee, Jian Su, Jen-Jen Su","doi":"10.1002/prp2.70212","DOIUrl":"10.1002/prp2.70212","url":null,"abstract":"<p><p>Pembrolizumab, an immune checkpoint inhibitor (ICI), has transformed cancer treatment across various malignancies, including metastatic urothelial cancer. As the use of pembrolizumab becomes increasingly widespread, understanding its potential adverse effects is essential. Here, we present the case of a 79-year-old male with urothelial cancer of the bladder, who experienced local recurrence after surgery and conventional therapies. He subsequently began pembrolizumab treatment. Following the first infusion, the patient developed a series of complications over a span of 26 days, including acute hepatitis, chest pain, and progressive bilateral ptosis. A third-degree atrioventricular block was also detected, necessitating pacemaker implantation. Further neurophysiological evaluations confirmed a diagnosis of myasthenia gravis and myositis. The patient was treated with intravenous methylprednisolone, immunoglobulin therapy, and pyridostigmine bromide. Despite these interventions, his condition deteriorated, requiring intubation and mechanical ventilation 28 days post-treatment. This case highlights that pembrolizumab can trigger rare but severe neurological and cardiovascular adverse events. Prompt and thorough investigations to identify syndromes such as myocarditis-myositis-myasthenia gravis overlap syndrome (IM3OS) are vital for timely diagnosis and intervention.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 1","pages":"e70212"},"PeriodicalIF":2.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12833557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046373","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}

{"title":"RETRACTION: Ivermectin Synergizes Sorafenib in Hepatocellular Carcinoma via Targeting Multiple Oncogenic Pathways.","authors":"","doi":"10.1002/prp2.70222","DOIUrl":"10.1002/prp2.70222","url":null,"abstract":"","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 1","pages":"e70222"},"PeriodicalIF":2.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12905504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146195394","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}

{"title":"Pharmacokinetics and Customized Dosing of Vancomycin in Adult Patients With Hematological Malignancies: Status, Challenges, and Opportunities.","authors":"Xiangqing Song, Meizi Zeng, Tao Yang, Mi Han","doi":"10.1002/prp2.70218","DOIUrl":"10.1002/prp2.70218","url":null,"abstract":"<p><p>Vancomycin (VAN) remains the first-line treatment for methicillin-resistant, multidrug-resistant gram-positive bacterial infections, even among cancer patients. Patients with hematological malignancies (HMs) represent a unique population, whose physiological and pathological changes often differ from those of the general population. These variations may cause significant alterations in the in vivo pharmacokinetics (PK) of VAN, causing unpredictable changes in the safety, efficacy, and bacterial resistance. Customized dosing of VAN (CD_van) offers potential solutions to these challenges. However, there is currently a lack of guideline-based, consensus-driven references, and limited research on the implementation of CD_van in HM patients, particularly in adults. This review concentrates on adult HM patients and reviews studies on VAN PK in them (including population PK and its models), focusing on current mainstream and novel CD_van technologies, including therapeutic drug monitoring-guided, model-guided, closed-loop control systems, and artificial intelligence-guided CD_van technologies. The challenges faced in the broader implementation of these technologies and the promising solutions exploited, such as blockchain technology-driven clinical decision support systems, are also discussed. Understanding the multifaceted aspects of PK research and personalized dosing of VAN in HM patients will help facilitate the rational treatment of VAN, in-depth PK research, and the development of CD_van techniques in HM patients.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 1","pages":"e70218"},"PeriodicalIF":2.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12859171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146093546","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}

{"title":"The Risk Factors and Mortality Among Patients With Different Combination Patterns of Opioids and Benzodiazepines: A Retrospective Study.","authors":"Fang-Yu Su, Ming-Che Tsai, Yee-Yung Ng, Shiao-Chi Wu","doi":"10.1002/prp2.70215","DOIUrl":"10.1002/prp2.70215","url":null,"abstract":"<p><p>The concurrent use of opioids and benzodiazepines (BZDs) has raised safety concerns due to increased risks of respiratory depression and death. To evaluate mortality risks linked to different patterns of co-prescription, we conducted a retrospective cohort study using data from a private hospital system between 2008 and 2018. A total of 418 549 opioid users were classified into four groups based on BZD use: opioids only, past use, continuous use, and new initiation. Cox proportional hazards regression model was used to estimate adjusted hazard ratios (aHRs) for 1-year all-cause mortality following 1-year of concomitant use, adjusting for past medical history and Charlson Comorbidity Index (CCI). Compared to the opioids-only group, mortality risks were significantly higher in the continuous (aHR = 1.78), new (aHR = 1.56), and past BZD use groups (aHR = 1.29). Higher mortality was also associated with older age, cancer, and greater comorbidity burden. These findings emphasize the need for cautious prescribing of opioids and BZDs, especially in older adults and those with complex medical conditions.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 1","pages":"e70215"},"PeriodicalIF":2.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12808813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145990227","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}

{"title":"Peripheral Neuropathy Associated With Proteasome Inhibitors and Immunomodulatory Drugs: A Pharmacovigilance Disproportionality Analysis Using VigiBase.","authors":"Letícia Penna Braga, Cristiane Aparecida Menezes de Pádua, Iwyson Henrique F da Costa, Paula Lana de Miranda Drummond, Pedro Henrique Carvalho de Souza, Laura Beatriz Fonseca, Marina Alacoque Rodrigues, Jéssica Soares Malta, Adriano Max Moreira Reis","doi":"10.1002/prp2.70191","DOIUrl":"10.1002/prp2.70191","url":null,"abstract":"<p><p>Immunomodulatory drugs (IMIDs) and proteasome inhibitors (PIs) are part of the frontline treatment landscape for multiple myeloma (MM). Despite their effectiveness, these drugs are associated with adverse effects, particularly clinically significant drug-induced peripheral neuropathy. The aim of this study was to evaluate the association between peripheral neuropathy and IMIDs and PIs used in MM, stratified by type of nerve dysfunction. VigiBase, the World Health Organization's global database of individual case safety reports (ICSRs), was analyzed. All ICSRs reported from 1 December 2001 to 31 May 2023 were extracted. Peripheral neuropathy cases were identified using MedDRA-preferred terms (neuropathy peripheral, autonomic neuropathy, peripheral motor neuropathy, peripheral sensory neuropathy) and standardized MedDRA queries (SMQ: peripheral neuropathy). Disproportionality signals were assessed using the reporting odds ratio (ROR) and information component (IC). Associations with peripheral neuropathy were found for all IMIDs and PIs. Both IMIDs and PIs were associated with peripheral sensory neuropathy. Associations with autonomic neuropathy were observed for bortezomib (ROR 12.90; 95% CI: 9.01-18.47), ixazomib (ROR 19.01; 95% CI: 7.89-45.80), carfilzomib (ROR 9.35; 95% CI: 3.01-29.10) thalidomide (ROR 8.86; 95% CI: 4.21-18.70). Associations with peripheral motor neuropathy were detected for bortezomib (ROR 63.87; 95% CI: 51.78-78.80), thalidomide (ROR 30.62; 95% CI: 22.67-41.40), lenalidomide (ROR 2.95; 95% CI: 2.11-4.14), pomalidomide (ROR 5.03; 95% CI: 2.91-8.69). Signals of autonomic neuropathy were identified for bortezomib, carfilzomib, ixazomib, and thalidomide, while signals of peripheral motor neuropathy were observed for bortezomib, thalidomide, lenalidomide, and pomalidomide. Associations with peripheral sensory neuropathy were detected for all IMIDs and PIs analyzed.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 6","pages":"e70191"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12678056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145678442","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}

{"title":"Effects of Botrychium ternatum (Thunb) Sw. On Cytochrome P450 Activities in Rats.","authors":"Jiange Yao, Liming Hu, Quan Zhou, Abdullah Al Mamun, Shuanghu Wang, Aixia Han","doi":"10.1002/prp2.70188","DOIUrl":"10.1002/prp2.70188","url":null,"abstract":"<p><p>Drug interactions commonly occur through the activities of cytochrome P450 (CYP). In this study, we evaluated the effects of the Chinese herbal medicine Botrychium Ternatum (Thunb) Sw. (BT) on six CYP enzymes. Twelve healthy male Sprague-Dawley rats were randomly divided into two groups (n = 6 each), which were administered the same doses of the probe drugs via gavage. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was performed to detect the plasma concentrations of the probe drugs and their metabolites. Serum biochemical indicators in rats were analyzed to determine the effect of BT on hepatocytes and their anabolism. Real-time fluorescence quantitative PCR was performed to assess the expression level of enzymes. The BT group showed lower AUC_(0-t) values and higher clearance rates for the probe drugs compared with the control group. Additionally, BT significantly increased the expression of six enzymes and decreased the levels of aspartate aminotransferase in rats. Therefore, dosage adjustment should be considered when patients are administered adjuvant BT-extract-containing drugs in combination with other drugs that are metabolized by the cytochrome P450 (CYP) enzymes.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 6","pages":"e70188"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12628597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145549987","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}

{"title":"Unbiased microRNA-Disease Association Prediction Using ICD-11 Codes and Negative Sampling.","authors":"Munyoung Chang, Jeonghee Jo, Junyong Ahn, Bong Gyun Kang, Sun Mo Nam, Chul-Kee Park, Sungroh Yoon","doi":"10.1002/prp2.70192","DOIUrl":"10.1002/prp2.70192","url":null,"abstract":"<p><p>We developed a computational model, called \"Unbiased microRNA-disease association predictor (UBMDA),\" to predict microRNA-disease associations. UBMDA has two major differences from those reported previously. First, we did not apply a similarity-based feature extraction method, which is the main basis of previous studies. Instead, we used International Classification of Diseases 11th Revision disease codes and microRNA nucleotide sequences as input features. Thus, UBMDA can be applied to newly discovered or poorly studied microRNAs and diseases. Second, we constructed an appropriate negative sample dataset. A positive sample dataset consisting of microRNAs and diseases pairs with proven associations between microRNAs and diseases is publicly available. However, datasets reporting no associations between microRNAs and diseases are rare. Therefore, a negative sample dataset was created by combining microRNAs and diseases. Because more commonly studied microRNAs and diseases are more likely to be included in the positive sample dataset, creating a negative sample dataset without taking this bias into consideration could cause an imbalance in disease and microRNA frequencies between positive and negative sample datasets, leading to biased prediction. To prevent such an imbalance, we created a negative sample dataset considering the frequency of each microRNA and disease in the positive sample dataset, such that these frequencies were similar between the negative and positive sample datasets. We successfully developed a computational model with a simple and intuitive structure. UBMDA will contribute to accelerating the development of microRNA-related biomarkers and therapeutics.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 6","pages":"e70192"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12661550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145637657","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}

{"title":"Effect of Thrombopoietin Receptor Agonist Romiplostim on the Ionizing Radiation-Induced Premature Aging.","authors":"Masaru Yamaguchi, Tokuhisa Hirouchi, Yoshiaki Sato, Ikuo Kashiwakura","doi":"10.1002/prp2.70203","DOIUrl":"10.1002/prp2.70203","url":null,"abstract":"<p><p>Environmental stressors, such as ionizing radiation, accelerate aging by causing DNA damage and triggering pathways that lead to cell cycle arrest, apoptosis, and subsequent inflammation. The thrombopoietin receptor agonist romiplostim (RP), which is used as a clinical treatment for chronic idiopathic thrombocytopenic purpura and aplastic anemia, is known to be promising in reducing radiation-induced tissue damage. In this study, we established a mouse model of radiation-induced premature aging to evaluate the potential of RP in ameliorating this process. Female C57BL/6JJcl mice were subjected to total body irradiation with various irradiation schedules. Mice irradiated with 5 Gy every 4 weeks (total dose of 10 Gy over 2 months) showed a significant aging phenotype, including graying hair and elevated serum aging markers (CDKN2A/p16^INK4a, tumor necrosis factor-α (TNF-α), and C-reactive protein), compared with sham-irradiated controls. RP was intraperitoneally administered to the mouse model (10 μg/kg weekly or 50 μg/kg every 4 weeks). Treatment significantly reduced TNF-α levels by 15% and the area of graying body hair by 70%. Although bone marrow cell recovery was incomplete, spleen cell counts were significantly restored (2-fold) by 50 μg/kg RP, and SA-β-gal activity, a marker of cellular senescence, was also significantly suppressed by approximately 15%. These findings suggest that RP may partially ameliorate radiation-induced premature aging, providing a basis for future research addressing health issues associated with aging and radiation exposure.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 6","pages":"e70203"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12666149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145649033","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}