Pharmacology Research & Perspectives最新文献

{"title":"The Influence of CYP2B6, GSTP1, and SLCO1B1 Star Allele-Predicted Phenotypes and CBR1 Genetic Variants on Effectiveness Outcomes in Patients With Hepatocellular Carcinoma Receiving Doxorubicin via Transarterial Chemoembolization.","authors":"Sireen Abdul Rahim Shilbayeh, Omnia A Abd El-Baset, Mohammad A Alshabeeb, Abdalrhman Hamdan Alanizi, Naglaa F Khedr, Rehab H Werida","doi":"10.1002/prp2.70114","DOIUrl":"10.1002/prp2.70114","url":null,"abstract":"<p><p>We investigated the influence of CYP2B6, GSTP1, and SLCO1B1 star allele-predicted phenotypes and CBR1 variants on clinical outcomes in patients with HCC receiving DOX via TACE. A prospective cohort of patients with HCC underwent DOX therapy via TACE. Selected genes were genotyped in germline DNA samples from the final cohort (82 patients) via Axiom Precision Medicine Diversity (PMD) Research Array technology. The Kaplan-Meier (KM) method and Cox proportional hazards (CPH) model were employed to find independent clinical and genetic predictors of overall survival (OS) and progression-free survival (PFS) after TACE. Based on univariate and combined association analyses of genetic factors, the star alleles predicting the phenotypic status of three genes (CYP2B6, GSTP1, and SLCO1B1) did not significantly modify the response potential of DOX via TACE, as indicated by OS or PFS. Conversely, we found a novel association between two CBR1 polymorphisms (rs3787728 and rs1005695) and interindividual differences in OS and PFS. The presence of a heterozygous genotype (TC or CG at either locus, which were highly frequent in our cohort), probably with greater CBR metabolic activity, appeared to have an expressive influence by negatively modulating the consequences of DOX locoregional therapy on HCC by shortening the median OS (KM p = 0.02 and 0.04, respectively) and median PFS (KM p = 0.05 and 0.023, respectively) in comparison to those with other haplotypes. Exploratory PGx studies involving a wider HCC cohort and targeting more DOX-related genes are needed to replicate our findings. Trial Registration: NCT06313047 (Study Details | Pharmacogenetic of Doxorubicin in HCC. | clinicaltrials.gov).</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 3","pages":"e70114"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12098310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128287","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":"Functional Liver Cell-Based Platforms in Biomedical Research.","authors":"Zohreh Hashemian, Sara Taleahmad, Bahare Shokouhian, Mustapha Najimi, Massoud Vosough","doi":"10.1002/prp2.70128","DOIUrl":"10.1002/prp2.70128","url":null,"abstract":"<p><p>Recapitulating in vivo conditions of metabolism remains a challenging subject in biomedical research such as ADME-Tox assays (absorption, distribution, metabolism, excretion, and toxicity). The advanced technologies using 3D co-culture methods enabled researchers to develop cell-cell and cell-extracellular matrix (ECM) interactions similar to the natural liver, resulting in the improvement of the metabolic performance of ex vivo cultured primary hepatocytes (PHs). Although PHs are the best candidates in cell-based drug screening methods, access to these cells is limited. The application of stem cell-derived hepatocyte-like cells (HLCs) could overcome these limitations in high-throughput assessments. However, the functional capacity of HLCs is not enough. Hepatoma cells could be reliable substitutes for PHs and HLCs; however, compared to PHs, their metabolic performance is low. Mimicking the complexity of the liver microenvironment using hepatoma cells and liver-specific stromal cells in a 3D culture condition represents an innovative, accessible, and scalable platform to accelerate drug development if the metabolic capacity of hepatoma cells is enhanced. This can reduce time, costs, and address the ethical concerns related to animal models and pluripotent stem cells. In this manuscript, we showed that mimicking the complexity of the liver microenvironment in a 3D co-culture condition with non-parenchymal cells and improving the metabolic performance of hepatoma cells represents an innovative and accessible platform to accelerate drug discovery and development.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 3","pages":"e70128"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209117","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":"Colo-Protective Effects of Pentoxifylline Alone or in Combination With Mesalamine in Colitis Through Sphingosine Kinase 1/Sphingosine 1 Phosphate, and Zonula Occuldin 1 Pathways: New Molecular Approach.","authors":"Fatemah A Alherz, Mahmoud S Abdallah, Esraa M Mosalam, Mostafa M Bahaa, Thanaa A Elmasry, Mohamad A El-Gammal, Walaa A Negm, AyaIbrahim Elberri, Nora Elshorbagi, Hend E Abo Mansour, Amir O Hamouda, Muhammed M Salahuddin, Mohamed Yasser, Mamdouh Eldesoqui, Sarah Alrubia, Amsha S Alsegiani, Eman El-Khateeb, Mohamed Kh ElMahdy, Eman Wahsh","doi":"10.1002/prp2.70115","DOIUrl":"10.1002/prp2.70115","url":null,"abstract":"<p><p>Multiple signaling pathways have been implicated in the pathogenesis of ulcerative colitis (UC), including Sphingosine Kinase 1 (SPHK)/Sphingosine-1-Phosphate (S1P), AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/NLR family pyrin domain-containing 3 (NLRP3), zonula occludens-1 (ZO-1), and signal transducer and activator of transcription 3 (STAT3). We aimed to investigate the Colo protective and anti-ulcerative effects of pentoxifylline (PTX) in a rat model of UC. Colitis was induced by intracolonic administration of 2 mL of 3% (v/v) acetic acid (AA). Thirty-five rats were randomly assigned to five groups (n = 7 each): normal control, colitis, mesalamine, PTX, and a combination of PTX plus mesalamine. Disease activity was assessed using the disease activity index, colon weight and length measurements, histological examination, and immunohistochemical detection of caspase-3. Colonic tissue homogenates were analyzed for interleukin-6 (IL-6), S1P, SPHK, mTOR, heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor 2 (Nrf2), AMPK, and STAT3 levels. Gene expression of ZO-1 and NLRP3 was also evaluated. Intracolonic AA induced marked functional, biochemical, and inflammatory damage to colonic tissue. Treatment with PTX, mesalamine, or their combination significantly attenuated these effects. Specifically, all treatments reduced levels of IL-6, S1P, SPHK, mTOR, STAT3, NLRP3, and caspase-3, while increasing levels of ZO-1, HO-1, Nrf2, and AMPK. The combination treatment group exhibited near-complete restoration of normal colonic architecture, characterized by intact crypt morphology and minimal fibrosis in the lamina propria. PTX attenuated inflammation, apoptosis, and oxidative stress in colitis, supporting its potential as an adjuvant therapy in UC management.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 3","pages":"e70115"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094538","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":"Supporting Pediatric RSV Clinical Trials Through Close Epidemiological Surveillance During the SARS-CoV-2 Pandemic.","authors":"Rennie Joshi, Georges J Nahhas, Carmen S Arriola, Patricia Saddier, Andrea Guerra","doi":"10.1002/prp2.70112","DOIUrl":"10.1002/prp2.70112","url":null,"abstract":"<p><p>Clesrovimab, an extended half-life monoclonal antibody, aims to protect infants for an entire RSV season. The pandemic impacted RSV epidemiology and strategies were implemented to support clesrovimab trials. Near real-time monitoring of data showed minimal RSV activity in 2020. In 2021, RSV resurged early in some countries and was delayed in others, resulting in a change in trial enrollment strategy.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 3","pages":"e70112"},"PeriodicalIF":2.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12045791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026270","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":"Trends in Lipid-Lowering Agent Consumption in Croatia: A 25-Year Observational Study.","authors":"Andrej Belančić, Marta Kučan Štiglić, Luka Prgomet, Ivan Pećin, Željko Reiner, Dinko Vitezić","doi":"10.1002/prp2.70122","DOIUrl":"10.1002/prp2.70122","url":null,"abstract":"<p><p>Cardiovascular diseases are the leading cause of mortality worldwide, with dyslipidemia as a major modifiable risk factor. This study aimed to assess 25-year trends in lipid-lowering agent consumption in Croatia from 2000 to 2023. We conducted a population-based analysis using IMS and IQVIA databases, calculating drug utilization in defined daily doses per 1000 inhabitants per day (DDD/1000) and evaluating financial expenditures and prescribing patterns. Over the study period, total lipid-lowering drug consumption increased more than 30-fold, from 4.91 DDD/1000 in 2000 to 152.56 DDD/1000 in 2023. Statins, particularly atorvastatin and rosuvastatin, drove this trend, while the uptake of PCSK9 inhibitors and ezetimibe reflected an evolving therapeutic landscape. Financial expenditures peaked in 2010, declined until 2015, and rose again by 2023, with average drug prices per DDD decreasing significantly. The observed increase in lipid-lowering therapy correlated with enhanced adherence to international guidelines and expanded patient access. However, administrative barriers and restrictive reimbursement policies continue to limit optimal utilization of newer agents. These findings underscore the importance of evidence-based policy development to address clinical inertia and improve cardiovascular outcomes in Croatia.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 3","pages":"e70122"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12086369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094554","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":"Costs of Treating Onasemnogene Abeparvovec-Xioi-Induced Liver Injury.","authors":"Andrej Belančić, Branislava Raičević, Ivana Stević, Dinko Vitezić, Slobodan M Janković","doi":"10.1002/prp2.70134","DOIUrl":"10.1002/prp2.70134","url":null,"abstract":"<p><p>Aims were to reveal types of onasemnogene abeparvovec-xioi (OA)-induced liver injury, their treatment patterns, utilization of healthcare, and treatment costs. This study employed secondary research to analyze OA-induced liver injury using data from the EudraVigilance database, published case reports, cohort studies, and clinical trials. The extracted data were analyzed to define real-life clinical entities that could be clearly outlined as syndromes resulting from the OA-induced liver injury, and further used in guiding the development of healthcare utilization matrices. Serbian healthcare costs were calculated by multiplying utilization figures by local unit prices, converted to Euros using exchange rates and adjusted by price level indices. A spreadsheet model with uniform distributions simulated costs for 1000 virtual patients, providing mean values and standard deviations for Serbia and the EU. From 1566 adverse event reports in the EudraVigilance database following OA therapy, 231 were hepatobiliary disorders, predominantly hypertransaminasaemia (30.7%; 71/231). Liver injury largely manifested as mild-to-moderate biochemical abnormalities, rarely progressing to severe complications, and was effectively managed with corticosteroid therapy. Economic analysis highlights the manageable burden of OA-induced liver injury. In the EU, mild-to-moderate cases cost €823.7, while severe cases average €1638.6. Medication costs range from €26.8 for prednisone to €695.4 for severe cases requiring additional immunosuppressive agents like tacrolimus and mycophenolate mofetil. To conclude, OA-induced liver injury, though notable, is clinically manageable with immunosuppressive therapy and rarely causes severe complications like encephalopathy or liver failure. Its modest costs do not undermine OA's cost-effectiveness, supporting its transformative role in spinal muscular atrophy treatment.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 3","pages":"e70134"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144286110","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":"Assessing Medication Adherence to Tadalafil 5 mg Once Daily in Erectile Dysfunction: A Cross-Sectional Analysis.","authors":"Emre Kandemir, Onur Kucuktopcu","doi":"10.1002/prp2.70129","DOIUrl":"10.1002/prp2.70129","url":null,"abstract":"<p><p>Our study aimed to examine medication adherence (MA) to tadalafil 5 mg once daily (OaD) in patients undergoing treatment for erectile dysfunction (ED) and to identify factors contributing to potential drug noncompliance. This cross-sectional study included 233 patients diagnosed with ED. Sociodemographic and clinical data were recorded. MA was assessed using the Medication Adherence Report Scale (MARS). Additionally, the Brief Illness Perception Questionnaire (B-IPQ), the Beliefs about Medicines Questionnaire (BMQ), and the International Index of Erectile Function (IIEF) were employed to evaluate patients' perceptions and beliefs regarding their condition and treatment. The influence of these factors on MA was thoroughly analyzed. High MA was reported in 136 (58.4%) of 233 patients. Factors, such as education level, monthly income, frequency of medical examinations, smoking habits, and a history of radical pelvic surgery, were found to influence MA (p < 0.05) significantly. Multivariate analysis identified monthly income and radical pelvic surgery history as statistically significant predictors of adherence (p ≤ 0.05). Additionally, adherence was significantly associated with IIEF scores, five items on the B-IPQ, and the BMQ subscales, including specific concerns, necessity, and general harm (p < 0.05). Tadalafil OaD demonstrates acceptable rates of MA in the treatment of ED. Socioeconomic and clinical factors, patients' cognitive and sensory status, and perceptions regarding medications and healthcare providers significantly influence adherence. Physicians should exercise caution when prescribing tadalafil 5 mg OaD to patients with lower socioeconomic status, as they may be at higher risk for reduced MA.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 3","pages":"e70129"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192121","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":"Comparative Efficacy of Different Targeted Therapies in Patients With Moderate-to-Severe Ulcerative Colitis: Systematic Review/Network Meta-Analysis and Mechanistic Overview.","authors":"Youran Dai, Wenhui Yang, Li Xu, Pingting Pan, Shan Liu, Yingzhe Sun, Suying Hu, Qiushuang Li, Fang Hu","doi":"10.1002/prp2.70108","DOIUrl":"10.1002/prp2.70108","url":null,"abstract":"<p><p>Ongoing evaluations of targeted therapies for moderate-to-severe ulcerative colitis (UC) continue to unfold, with the emergence of novel drugs. However, head-to-head trials comparing these therapies are still lacking. The aim of this study is to investigate the therapeutic effects of targeted therapies in moderate-to-severe UC. The Cochrane Library, Web of Science, PubMed, and Embase were searched from the inception to November 12, 2024. Statistical analyses included multivariate random effects models and Bayesian modeling. Stratified and sensitivity analyses were also performed. Publication bias was assessed using funnel plots. Outcomes such as clinical response/remission, endoscopic remission, mucosal healing, quality of life, adverse events (AEs), and serious adverse events (SAEs) were used to quantify the relative therapeutic effects. Thirty-three studies (33 reported on the induction phase; 13 reported on the maintenance phase) were identified. In the induction phase, Upadacitinib 45 mg demonstrated the highest efficacy in achieving clinical remission (OR 10.03; 95% CI, 4.83-20.80), clinical response (OR 7.96; 95% CI, 3.89-16.28), and mucosal healing rate (OR 8.91; 95% CI, 3.36-23.62). Cobitolimod 250 mg was the first-ranked treatment (SUCRA, 92.67%) in Endoscopic remission. Vedolizumab 108 mg was the best dosage in reducing Adverse Events (AEs). The optimal dosage for reducing Serious Adverse Events (SAEs) was found to be Tulisokibart 1000/500 mg. During the maintenance phase, Etrasimod 2 mg/kg ranked first in clinical remission (OR 9.58; 95% CI, 2.82-32.59), and Upadacitinib 45 mg was superior in endoscopic remission. Additionally, the most effective medication for raising quality of life was Guselkumab 200 mg (OR 3.04; 95% CI, 1.70-5.40). Consequently, there is a need for further high-quality research to conclusively determine the best therapeutic option.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 3","pages":"e70108"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12138205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226189","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":"Pharmacokinetic Properties and Therapeutic Effectiveness of Remimazolam in ICU Patients With Mechanical Ventilation: A Preliminary Study.","authors":"Jing Hu, Yuhan Zhao, Litao Shao, Wenhui Zhang, Han Wang, Yun Liu, Mengxiang Su, Xiangrong Zuo","doi":"10.1002/prp2.70130","DOIUrl":"10.1002/prp2.70130","url":null,"abstract":"<p><p>The pharmacokinetic (PK) profile of remimazolam, a ultra-short-acting benzodiazepine, has been investigated for procedural sedation and anesthesia, but its pharmacokinetics, pharmacodynamics, and optimal dosing for ICU sedation are still unclear. This prospective, single-center, double-blind randomized controlled trial studied ICU adults on mechanical ventilation for over 24 h. Participants were divided into three groups, each receiving a 0.2 mg/kg remimazolam loading dose in less than a minute, followed by maintenance doses of 0.1, 0.3, or 0.5 mg/kg/h. Plasma concentrations of remimazolam and its metabolites were measured using UPLC-MS/MS, and pharmacokinetic parameters were calculated using one-compartmental methods with WinNolin. The study also assessed pharmacodynamic indicators (RASS score) and the impact of the clinical indicators on pharmacokinetic parameters. The study on 36 ICU patents using a one-compartment model found that after 24 h of continuous intravenous remimazolam infusion, the drug had a median clearance rate of 22.23 mL/kg/min and a volume of distribution of 2656.58 mL/kg. The half-life was 101.791 min in ventilated patients, while its metabolites had a slower clearance rate of 0.49 mL/kg/min and an longer half-life of 656.02 min. Sedation levels were mild to moderate at dosed of 0.1-0.3 mg/kg/h. Liver function significantly affected remimazolam metabolism, influencing the half-life (R² = 0.36, p = 0.00013) and clearance (R² = 0.13, p = 0.04). The pharmacokinetic study indicates that remimazolam is effective and safe for ICU patients on mechanical ventilation, with a 24-h infusion demonstrating rapid clarence and a clear dose-effect relationship. It provides mild to moderate sedation at 0.1-0.3 mg/kg/h, but caution is advised for patients with severe liver dysfunction due to its impact on drug metabolism. Trial Registration: ClinicalTrials.gov identifier: NCT05480787.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 3","pages":"e70130"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12167508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302709","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":"Encapsulation of Carvedilol in Nanomicelles Improves Central Hemodynamics and Target Organ Damage Protection in Spontaneously Hypertensive Rats.","authors":"Luciano Parola, Paula Denise Prince, Javier Alberto Walter Opezzo, Jennifer Riedel, Miguel Ángel Allo, Yanina Alejandra Santander Plantamura, Eliana P Bin, Germán E González, Andrea Carranza, Martín Donato, Diego A Chiappetta, Marcela A Moretton, Christian Höcht","doi":"10.1002/prp2.70125","DOIUrl":"10.1002/prp2.70125","url":null,"abstract":"<p><p>The hypothesis of this work was that chronic treatment with carvedilol (CAR) administered in a nanomicelles-based formulation (CAR-NMs), which increases CAR oral bioavailability, is more effective than a conventional liquid CAR formulation (CAR-LCF) and is comparable to chronic treatment with losartan (LOS) in improving hemodynamic parameters and preventing target organ damage (TOD) in spontaneously hypertensive (SH) rats. Chronic treatment with CAR-NMs significantly improved central hemodynamic parameters (systolic and diastolic blood pressure (BP) and its variability) to a similar extent as LOS, and with superior efficacy than CAR-LCF. Although LOS was more effective than CAR-NMs and CAR-LCF in reducing peripheral systolic BP, both LOS and CAR-NMs, in contrast to CAR-LCF, were able to significantly reduce short-term BP variability indexes. Both CAR formulations and LOS significantly reduced aortic media wall thickness and interstitial collagen deposition, and lowered TNF-α expression in left ventricle (LV) in SH rats. Only CAR-NMs significantly reduced IL-6 expression and were more effective in reducing ventricular TGF-β expression in LV of SH rats. These findings suggest that encapsulation of CAR in NMs improved its ability to control central hemodynamics in SH rats when compared with CAR-LCF, mainly due to a greater effect on carotid systolic BP and short-term BP variability, resulting in a higher protection against TOD compared to CAR-LCF.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 3","pages":"e70125"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12127884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199852","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}