Pharmacological Reports最新文献

{"title":"Unveiling hidden risks: pharmacogenetic insights from a cross-sectional study of statin therapy in the Indian population.","authors":"Shaik Mohammad Naushad, Palani Kumar Palanichamy, Jagadeesh Babu Sreemanthula, Yadam Reddy Kanaka Durga Devi, Palakonda Gopi, Tajamul Hussain, Vijay Kumar Kutala","doi":"10.1007/s43440-025-00746-1","DOIUrl":"https://doi.org/10.1007/s43440-025-00746-1","url":null,"abstract":"<p><strong>Background: </strong>Statin usage has increased significantly in India due to the very high incidence of dyslipidemia, however, approximately 18% of the population is at risk for statin-induced myopathy. Hence, we conducted a population-level screening for pharmacogenetic determinants of statin therapy, particularly Solute Carrier Organic Anion Transporter Family Member 1B1 (SLCO1B1) and ATP-binding cassette sub-family G member 2 (ABCG2).</p><p><strong>Materials and methods: </strong>Whole exome sequencing was performed in 2180 subjects, and the variant data were segregated further into diplotypes and phenotypes.</p><p><strong>Results: </strong>SLCO1B1 normal function was observed in 81% of subjects (diplotypes: 1/*1, *1/*14, *1/*20, *1/*37, and *37/*37). Increased SLCO1B1 function was observed in 8% of the population (diplotypes: *14/*14 and *20/*20). Decreased function of SLCO1B1 (*1/*15) was observed in 5% of the population. Poor function of SLCO1B1 was observed in 6% of the population (diplotypes: *5/*5 and *15/*15). About 81.46% of subjects displayed normal ABCG2 function, while 17.34% had decreased and 1.19% had poor function. Combined SLCO1B1/ABCG2 functional defects were observed in 7.4% of subjects. Two rare SLCO1B1 variants in SLCO1B1 i.e., rs201722521 and rs71581988, were reported to affect the binding affinity of certain statins. The SLCO1B1 C-C-C-A-A-A haplotype was associated with a 2.22-fold risk for hyperbilirubinemia (95% CI: 1.13-4.36, p = 0.02). Rosuvastatin's daily dose of up to 10 mg is well tolerated across the different SLCO1B1 functionality groups.</p><p><strong>Conclusions: </strong>This study demonstrates that 11% of our population exhibit decreased or poor function of SLCO1B1 and 7.4% exhibit decreased or poor function of both SLCO1B1 and ABCG2, necessitating adjustments in daily statin doses to minimize the risk for statin-induced myopathy.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Residence time in drug discovery: current insights and future perspectives.","authors":"Szymon K Kordylewski, Ryszard Bugno, Sabina Podlewska","doi":"10.1007/s43440-025-00748-z","DOIUrl":"https://doi.org/10.1007/s43440-025-00748-z","url":null,"abstract":"<p><p>The temporal stability of ligand-receptor complexes is increasingly acknowledged as a critical factor in drug discovery, influencing both efficacy and pharmacodynamics. Although the relationship between the duration of compound action and complex stability can be traced back to Paul Ehrlich's 19th-century doctrine Corpora non agunt nisi fixata, its significance has gained renewed attention in recent years. This review comprehensively examines the concept of residence time (RT). We first summarize key ligand binding models (lock-and-key, induced-fit, and conformational selection) and delve into various perspectives on how RT impacts functional outcomes. Furthermore, we discuss experimental methods for measuring RT, highlighting both radioligand and non-radioligand approaches. The growing interest in RT has spurred advancements in computational techniques, particularly molecular dynamics simulations, which utilize diverse strategies to observe dissociation events. We outline these molecular dynamics-based methods, their theoretical foundations, and provide examples of their application in assessing RT. Finally, we highlight molecular determinants of prolonged RT, focusing primarily on G protein-coupled receptors (GPCRs) while also incorporating relevant data from other receptor classes.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of curcumin on vascular smooth muscle cells: implications for health and disease.","authors":"Majid Shohrati, Farshad Abedi, Mahdi Bagheri, Amirhossein Sahebkar","doi":"10.1007/s43440-025-00744-3","DOIUrl":"https://doi.org/10.1007/s43440-025-00744-3","url":null,"abstract":"<p><p>Vascular smooth muscle cells (SMCs) are pivotal in regulating vascular tone and integrity. Their dysregulation significantly contributes to the pathophysiology of cardiovascular ailments, including atherosclerosis, blood pressure, and vascular remodeling. Curcumin, a polyphenol with a natural origin in turmeric, exhibits promising therapeutic properties due to its remarkable anti-inflammatory, antioxidant, and antiproliferative characteristics. This review aims to assess the effects of curcumin on vascular SMC behavior, encompassing its impact on proliferation, migration, phenotypic switching, and extracellular matrix remodeling. The underlying molecular mechanisms are highlighted, particularly curcumin's modulation of signaling pathways such as nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and nuclear transcription factor E2-related factor-2 (Nrf2) signaling pathways, as well as its ability to decrease oxidative stress and inflammatory cytokine generation. Furthermore, we evaluate the implications of the results for vascular health and disease, emphasizing curcumin's potential to prevent or mitigate atherosclerosis, restenosis, and hypertension. Despite promising preclinical evidence, challenges related to curcumin's bioavailability and clinical translation remain.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel receptor tyrosine kinase-targeted strategies to overcome resistance in oral squamous cell carcinoma.","authors":"Shahryar Irannejadrankouhi, Hassan Mivehchi, Aisan Eskandari-Yaghbastlo, Seyedeh Tabasom Nejati, Sahand Emrahoglu, Fatemeh Azarang, Abbas Nikroo, Mohsen Nabi-Afjadi","doi":"10.1007/s43440-025-00745-2","DOIUrl":"https://doi.org/10.1007/s43440-025-00745-2","url":null,"abstract":"<p><p>Treatment for oral squamous cell carcinoma (OSCC) has seen the rise of receptor tyrosine kinase inhibitors (RTKIs). However, their therapeutic effectiveness is severely limited by the emergence of resistance. Epidermal growth factor receptor (EGFR)-independent survival pathways, extracellular vesicle (EV)-mediated drug sequestration, lysosomal exocytosis, and metabolic reprogramming mediated by METTL1 (methyltransferase-like protein 1) are some of the molecular and cellular mechanisms that underlie RTKI resistance in OSCC. In this line, specific resistance methods are carefully studied, including the signaling processes involving SHP2, the different ways ErbB2 and AKT, and features related to tumor stemness. Additionally, the interaction between resistance and the tumor microenvironment (TME), namely via EVs and modified angiogenic signaling, is emphasized. Novel therapy approaches are put forth to address these issues. The effectiveness of treatment may be improved by combination treatments that include RTKIs with other medications, such as mTOR inhibitors, chemotherapy, radiation, and immunotherapies. Innovative nanotechnology-based strategies, such as exosome-based drug carriers and liposomal drug delivery systems, provide encouraging answers for overcoming resistance and enhancing precise targeting. Furthermore, phytochemicals and herbal remedies are investigated as supplementary approaches to enhance RTKI responses. Despite the potential of these approaches, obstacles, including resolving tumor heterogeneity, limiting off-target effects, and improving delivery methods, continue to be major obstacles to clinical use. To inform personalized medicine strategies, future studies should concentrate on finding predictive biomarkers and conducting thorough preclinical validation. By integrating emerging therapies and addressing these limitations, this work provides a comprehensive foundation for advancing the management of OSCC and improving patient outcomes.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chalcone-9: a novel inhibitor of the JAK-STAT pathway with potent anti-cancer effects in triple-negative breast cancer cells.","authors":"Song-Hee Lee, Haeri Lee, Yong-Jin Kwon, Seul-Ki Kim, Eun-Bi Seo, Jie Ohn Sohn, Byung-Hak Kim, Jung-Youl Park, Sang-Kyu Ye","doi":"10.1007/s43440-025-00721-w","DOIUrl":"10.1007/s43440-025-00721-w","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer remains the leading cause of cancer incidence and mortality among women worldwide, with triple-negative breast cancer (TNBC) posing significant treatment challenges. The dysregulation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway contributes to tumor progression, making it a potential therapeutic target. Chalcones, known for their diverse biological activities, including anti-cancer effects, hold promise for drug development. This study explores the anti-cancer activity of (E)-4-(3-(2-(benzyloxy)-6-hydroxyphenyl)-3-oxoprop-1-en-1-yl)benzoic acid (chalcone-9), a novel chalcone derivative.</p><p><strong>Methods: </strong>The cytotoxic effects of chalcone-9 were evaluated in breast cancer cell lines, including TNBC lines MDA-MB-231 and MDA-MB-468. Western blotting and qRT-PCR were used to analyze the impact on JAK1, JAK2, STAT1, and STAT3 activation and their downstream gene expression. In silico molecular docking analysis was conducted to determine whether chalcone-9 can interact with JAK1 and JAK2. A wound healing assay was used to observe the effect of chalcone-9 on tumor cell migration, and flow cytometry was employed to analyze whether chalcone-9 inhibits tumor cell cycle progression and induces apoptosis. The expression of apoptosis markers was also assessed.</p><p><strong>Results: </strong>Chalcone-9 exhibited dose-dependent cytotoxicity in breast cancer cell lines, with TNBC cells showing higher sensitivity. Chalcone-9 effectively inhibited the activation of JAK1, JAK2, STAT1, and STAT3, outperforming conventional JAK/STAT inhibitors. The structure of chalcone-9 was confirmed to stably interact with JAK1 and JAK2 proteins. It also suppressed STAT1 and STAT3 target gene expression, reduced tumor cell migration, and induced apoptosis, as evidenced by PARP and caspase cleavage and decreased survivin levels.</p><p><strong>Conclusions: </strong>Chalcone-9 demonstrates significant anti-cancer activity, particularly against TNBC. By targeting the JAK/STAT pathway and promoting apoptosis, chalcone-9 emerges as a promising therapeutic candidate for aggressive breast cancers.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"761-774"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 magnolol on the liver antioxidant status in rats with diabetes.","authors":"Sławomir Dudek, Weronika Borymska, Maria Zych, Dżesika Chełminiak, Magdalena Kimsa-Dudek, Ilona Kaczmarczyk-Żebrowska","doi":"10.1007/s43440-025-00718-5","DOIUrl":"10.1007/s43440-025-00718-5","url":null,"abstract":"<p><strong>Background: </strong>Magnolol isolated from Magnolia (Magnolia sp.) flowers are used to support the treatment of diabetes. The aim of this study was to investigate the effects of magnolol on the liver antioxidant status in rats with type 2 diabetes and assess oxidative stress parameters at both biochemical and molecular levels.</p><p><strong>Methods: </strong>Mature male Wistar rats with high-fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetes were administered magnolol at doses of 5 or 25 mg/kg body weight po for 4 weeks. Then, the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), the concentrations of advanced protein oxidation products (AOPPs) and malondialdehyde (MDA), the total antioxidant response (TAR), and the total oxidative status (TOS) were assessed using commercially available colorimetric kits according to the manufacturers' protocols. The mRNA levels of the cytochrome P450 family 1 subfamily A member 2 (CYP1A2), cytochrome P450 family 2 subfamily E member 1 (CYP2E1), nuclear factor erythroid 2-related factor 2 (NFE2L2), and Kelch like ECH-associated protein 1 (KEAP1) genes were determined using real-time quantitative reverse transcription-polymerase chain reaction (RT‒qPCR). All parameters were analyzed in liver samples.</p><p><strong>Results: </strong>Compared with 5 mg/kg magnolol, 25 mg/kg magnolol had a more beneficial effect on several indicators of oxidative stress in the liver observed as significant decreases in the activity of SOD and CAT, as well as decreased MDA concentrations. Further, significant increases in the concentrations of AOPPs and native thiols were observed. The gene encoding CYP2E1 was upregulated in diabetic rats compared with control rats. Moreover, compared with diabetic rats, diabetic rats treated with 25 mg/kg magnolol presented increased expression of the KEAP1 gene.</p><p><strong>Conclusions: </strong>The induction of diabetes is known to disturb redox homeostasis. The administration of magnolol at the higher dose used in this study, might counteract the changes in the liver antioxidant status at both the molecular and biochemical levels. Owing to the positive alterations in some oxidative stress parameters, after further in-depth study, magnolol may be considered a promising compound that could be used to complement diabetes treatment.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"716-728"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High BMI predicts poor cancer pain relief when rotating from oral opioids to transdermal Fentanyl: a two-center retrospective study.","authors":"Ya Chen, Songling Han, Xiaogang Hu, Xue Ma, Yue Qiu, Yuelu Tang, Xiaoxiao Wang, Lixian Li, Chao Li, Wanyi Chen","doi":"10.1007/s43440-025-00723-8","DOIUrl":"10.1007/s43440-025-00723-8","url":null,"abstract":"<p><strong>Background: </strong>The analgesic effect of transdermal fentanyl (TDF) differs among cancer pain patients. This study aims to investigate the relationship between clinical factors and pain relief when using TDF in cancer pain patients who rotate from oral opioids to TDF.</p><p><strong>Methods: </strong>A two-center retrospective study was conducted in Chongqing University Cancer Hospital and Sichuan Cancer Hospital, including adult cancer pain patients who rotated from oral opioids to TDF between 2018 and 2022. Based on the clinical characteristics, logistic regressions and directed acyclic graphs (DAG) were employed to identify significant factors influencing the efficacy of TDF. The study adhered to STROBE guidelines.</p><p><strong>Results: </strong>This survey included 359 patients, among them, 254 patients (70.8%) attained good pain relief after rotating to TDF. 59.3% of patients utilized TDF at standard dosage, while 24.8% used underdose TDF, with only 52.8% achieving adequate pain relief, significantly lower than other groups (p < 0.001). Initial univariable analysis of 22 clinical factors among the standard dose group showed that a higher body mass index (BMI, median 23.2 kg/m² vs. 21.0 kg/m², OR = 0.83 [0.75-0.91], p < 0.001) and the presence of lung cancer (OR = 0.31 [0.11-0.89], p = 0.030) predicted potentially unsatisfactory pain control after TDF treatment. Subsequently, a multivariable regression analysis based on DAG-directed factor selection identified BMI (OR = 0.82 [0.74-0.92], adjusted p < 0.01) as the only independent factor influencing TDF effectiveness.</p><p><strong>Conclusions: </strong>Our study suggested that high BMI was a significant predictor of poor cancer pain relief when rotating from oral opioids to TDF, and provides a useful measurement of managing adult cancer pain when using TDF.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT06369961, registered on April 11, 2024; https://clinicaltrials.gov/study/NCT06369961 .</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":"77 3","pages":"789-799"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic liability for anxiety and treatment response to the monoamine stabilizer OSU6162 in alcohol dependence: a retrospective secondary analysis.","authors":"Mun-Gwan Hong, Lotfi Khemiri, Joar Guterstam, Johan Franck, Nitya Jayaram-Lindström, Philippe A Melas","doi":"10.1007/s43440-025-00707-8","DOIUrl":"10.1007/s43440-025-00707-8","url":null,"abstract":"<p><strong>Background: </strong>OSU6162, a monoamine stabilizer, has demonstrated efficacy in reducing alcohol and anxiety-related behaviors in preclinical settings. In a previous randomized, double-blind, placebo-controlled trial involving patients with alcohol dependence (AD), OSU6162 significantly reduced craving for alcohol but did not alter drinking behaviors. This retrospective secondary analysis explores whether genetic predispositions related to AD and associated traits might influence the response to OSU6162 treatment in original trial participants.</p><p><strong>Methods: </strong>Polygenic risk scores (PRSs) were calculated for 48 AD patients using PRSice-2 and genome-wide association study (GWAS) data for (i) alcohol use disorder and alcohol consumption, (ii) problematic alcohol use, (iii) drinks per week, (iv) major depression, and (v) anxiety (case-control comparisons and quantitative anxiety factor scores). Linear regression analyses, adjusted for population stratification, assessed interaction effects between PRSs and treatment type (OSU6162 or placebo) on various clinical outcomes.</p><p><strong>Results: </strong>Significant interactions were found between treatment type and anxiety factor score PRS at the genome-wide significance threshold. In the OSU6162-treated group, a higher anxiety PRS was associated with reductions in the number of drinks consumed (FDR = 0.0017), percentage of heavy drinking days (FDR = 0.0060), and percentage of drinking days (FDR = 0.0017), with a trend toward reduced blood phosphatidylethanol (PEth) levels (FDR = 0.068). These associations were absent in the placebo group.</p><p><strong>Conclusions: </strong>These preliminary findings suggest that anxiety PRS may help predict response to OSU6162 treatment in AD. Further research with larger cohorts and more comprehensive genetic data is needed to confirm these results and advance personalized medicine approaches for alcohol use disorder.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"840-849"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanisms underlying the effects of statins on bone metabolism: an evolving paradigm of statins delivery modalities for bone regeneration.","authors":"Randa Mohammed Zaki, Mohamed A M Ali, Mayada Said, Anis Ahmad Chaudhary, Fehmi Boufahja, Obaid Afzal, Abdelghafar M Abu-Elsaoud, Alyaa S Abdel Halim","doi":"10.1007/s43440-025-00716-7","DOIUrl":"10.1007/s43440-025-00716-7","url":null,"abstract":"<p><p>Statins, recognized for their lipid-lowering capabilities, have demonstrated osteoanabolic and anti-resorptive effects on bone metabolism. The effects encompass the overexpression of bone morphogenetic proteins, heightened osteoblast activity, and the control of inflammation. Nevertheless, conventional systemic administration of statins has difficulties, including restricted bone bioavailability and possible adverse effects. Recent improvements in targeted and localized drug delivery are revolutionizing the therapeutic landscape for statins in bone applications. This review consolidates existing knowledge regarding the molecular processes by which statins influence bone metabolism and describes novel drug delivery methods such as nano-carriers, biomaterial scaffolds, and controlled-release systems. It seeks to address current knowledge deficiencies and offer insights into how enhanced bioavailability and specificity can optimize the efficiency of statins in bone regeneration. The review integrates molecular insights with novel pharmacological strategies to inform future research and clinical applications, pinpointing critical areas for exploration, such as optimal dose, delivery safety, and clinical efficacy.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"624-644"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential drug-drug interactions analysis in Polish pediatric hemato-oncologic unit, including acute lymphoblastic leukemia patients.","authors":"Arkadiusz Adamiszak, Julia Drobińska, Izabela Niewiadomska-Wojnałowicz, Katarzyna Derwich, Edmund Grześkowiak, Agnieszka Bienert","doi":"10.1007/s43440-025-00719-4","DOIUrl":"10.1007/s43440-025-00719-4","url":null,"abstract":"<p><strong>Background: </strong>The lack of information on drug-drug interactions in the pediatric population significantly complicates making effective therapeutic decisions. Our study aimed to analyze the rate and risk factors as well as present potential drug-drug interactions (pDDIs) specifically for pediatric patients from the pediatric hemato-oncologic unit, including acute lymphoblastic leukemia (ALL) patients.</p><p><strong>Methods: </strong>We conducted a six-month prospective study in which clinical pharmacists examined medical records once a week to look for pDDIs using the Lexicomp^® Drug Interactions Checker. Spearman's rank coefficient, logistic regression, and the U-Mann-Whitney test were used to identify correlations, analyze risk factors for pDDIs, and compare ALL patients with non-ALL patients, respectively. Recommendations were provided for the D and X pDDIs categories.</p><p><strong>Results: </strong>We identified 507 pDDIs in 119 screened patients, 388 of which were clinically relevant. Nearly 68% of the patients were exposed to at least one significant interaction. The number of pDDIs was positively correlated with the number of medications (r_s=0.75, p < 0.001), off-label used drugs (r_s=0.42, p < 0.001), comorbidities (r_s=0.21, p = 0.019), and hospitalization length (r_s=0.48, p < 0.001). The multivariate analysis revealed that at least 7 administered medications (OR = 8.63; 95% CI = 2.92-25.47) and 13 days in the hospital (OR = 3.47; 95% CI = 1.31-9.19) were risk factors for pDDIs. Furthermore, patients treated for ALL represent an at-risk group with a statistically higher number of drugs taken and pDDIs identified.</p><p><strong>Conclusions: </strong>Limited data on drug-drug interactions in the pediatric population emphasizes the need for close collaboration between clinical pharmacists and clinicians to improve the safety and effectiveness of pharmacotherapy.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"751-760"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}