DARU Journal of Pharmaceutical Sciences最新文献

{"title":"Royal jelly and its hormonal effects in breast cancer: a literature review.","authors":"Farzaneh Aavani, Roja Rahimi, Pouya Goleij, Hossein Rezaeizadeh, Roodabeh Bahramsoltani","doi":"10.1007/s40199-024-00513-2","DOIUrl":"10.1007/s40199-024-00513-2","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is the most common cancer in women which can be cured in most individuals with early-stage non-metastatic disease. Imbalance in estrogen signaling pathways and propagating levels of estrogens has important roles in breast cancer development. Targeting the estrogen receptor signaling pathway is linked to breast cancer treatment. Royal jelly is one of the bee products containing 10-hydroxy-2-decenoic acid, a structure similar to mammalian estrogen, allowing it to attach to estrogen receptors. It is considered as a general tonic and immunomodulator which may be helpful in reducing the side effects of cancer treatments. Currently, there are controversial data regarding the pros and cons of royal jelly in cancer. Here we provide an overview of the effects of royal jelly on sex hormones and its possible role in breast cancer.</p><p><strong>Methods: </strong>Electronic databases including PubMed, Scopus, and Web of Science were searched with the search terms royal jelly, cancer, and sexual hormones. All preclinical and clinical studies regarding the hormonal effects of royal jelly were included.</p><p><strong>Results: </strong>According to the collected preclinical data, consumption of royal jelly at daily doses below 200 mg/kg can be useful to decrease the risk of breast cancer since it reduces the serum level of estrogen; whereas increases progesterone, which subsequently decreases the expression of ERs on the ER-positive cells.</p><p><strong>Conclusion: </strong>Future clinical studies are essential to confirm the safe dose of royal jelly as an adjuvant therapy in breast cancer.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"745-760"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876122","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":"Ameliorative effect of Melatonin on 5-Fluorouracil-induced reproductive toxicity in male rats.","authors":"Darya Almasi, Sohrab Kazemi, Mohammad Hossien Asghari, Seyed Mohammad Hosseini, Ali Akbar Moghadamnia","doi":"10.1007/s40199-024-00537-8","DOIUrl":"10.1007/s40199-024-00537-8","url":null,"abstract":"<p><p>5-Fluorouracil (5-FU) is an antimetabolite chemotherapeutic agent that can cause oxidative stress and complications in normal organs, including the reproductive system. This study was conducted to investigate the effect of melatonin (MEL) on 5-FU-induced reproductive toxicity in male rats. Male Wistar rats weighing 180 ± 20 g were divided into five groups: control, 5-FU (50 mg/kg), 5-FU + MEL (2.5, 5 & 10 mg/kg). The testes and prostates were removed, and histopathological aspects, biochemical markers, and gene expression were investigated. The effect of 5-FU on the normal TM4 cell line (murine testicular Sertoli line) and co-treatment of 5-FU and MEL were studied using MTT assay. Results showed that MEL prevented cell death in the TM4 cell line induced by 5-FU. MEL also reduced edema, hyperemia, and vacuolization in testis and prostate tissues induced by 5-FU. Additionally, MEL increased the activity of antioxidant enzymes and reduced the levels of MDA (p < 0.0001) and MPO (p < 0.0001). The levels of testosterone (p < 0.01) and the number of spermatocytes and spermatogonia (p < 0.0001) were increased in groups receiving 5-FU with MEL compared to 5-FU alone. The prostate-specific antigen (PSA) level in prostate samples was lower in the groups receiving 5-FU with MEL compared to the 5-FU group. Furthermore, the genes expression of COX-2 and TNF-α in testis tissues was reduced in the presence of MEL. in conclusion, the antioxidant property of MEL can protect the male reproductive system against 5-FU toxicity, as evidenced by the improved histopathological and biochemical parameters, as well as the reduced gene expression of COX-2 and TNF- α genes.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"675-687"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281698","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":"Preparation of poly(vinyl alcohol) nanofibers containing disulfiram-copper complex by electrospinning: a potential delivery system against melanoma.","authors":"Gomaa F El Fawal, Marwa M Abu-Serie","doi":"10.1007/s40199-024-00527-w","DOIUrl":"10.1007/s40199-024-00527-w","url":null,"abstract":"<p><strong>Background: </strong>Melanoma poses a significant threat to human health, making the development of a safe and effective treatment a crucial challenge. Disulfiram (DS) is a proven anticancer drug that has shown effectiveness when used in combination with copper (DS-Cu complex).</p><p><strong>Objectives: </strong>This study focuses on encapsulation of DS-copper complex into nanofiber scaffold from polyvinyl alcohol (PVA) (DS-Cu@PVA). In order to increase bioavailability towards melanoma cell lines and decrease its toxicity.</p><p><strong>Methods: </strong>The scaffold was fabricated through an electrospinning process using an aqueous solution, and subsequently analyzed using ART-Fourier transform infrared spectroscopy (ART-FTIR), scanning electron microscopy (SEM), and energy dispersive X-ray analysis (EDX). Additionally, cellular cytotoxicity, flow cytometry analysis, and determination of caspase 3 activity were conducted to further characterize the scaffold.</p><p><strong>Results: </strong>The results confirmed that encapsulation of DS-Cu complex into PVA was successful via different characterization. The scanning electron microscopy (SEM) analysis revealed that the diameter of the nanofibers remained consistent despite the addition of DS-Cu. Additionally, ATR-FTIR confirmed that the incorporation of DS-Cu into PVA did not significantly alter the characteristic peaks of PVA. Furthermore, the cytotoxicity assessment of the DS-Cu@PVA nanofibrous scaffold using human normal skin cells (HFB4) demonstrated its superior biocompatibility compared to DS-Cu-free counterparts. Notably, the presence of DS-Cu maintained its effectiveness in promoting apoptosis by increasing cellular reactive oxygen species, proapoptotic gene expression, and caspase 3 activity, while simultaneously reducing glutathione levels and oncogene expression in human and mouse melanoma cell lines (A375 and B16F10, respectively). Overall, these findings suggest that the addition of DS-Cu to PVA nanofibers enhances their biocompatibility and cytotoxic effects on melanoma cells, making them a promising candidate for biomedical applications.</p><p><strong>Conclusion: </strong>The findings indicate that the targeted delivery of DS-Cu onto a PVA nanofiber scaffold holds potential approach to enhance the efficacy of DS-Cu in combating melanoma.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"573-583"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497347","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":"Toxicological effect of acetaminophen, metamizole, and nimesulide cocktail on early development of zebrafish.","authors":"Wellington Fernandes de Carvalho, Ednalva de Souza Pereira Lima, Whocely Victor de Castro, Ralph Gruppi Thomé, Hélio Batista Santos","doi":"10.1007/s40199-024-00528-9","DOIUrl":"10.1007/s40199-024-00528-9","url":null,"abstract":"<p><strong>Background: </strong>Several countries' most incorrectly discarded medicines are acetaminophen (ACM), metamizole (MTZ), and nimesulide (NMS). These xenobiotics easily reach the aquatic environment; such contamination is very important for the health of humans and other species, yet little explored.</p><p><strong>Objectives: </strong>To evaluate the cocktail effect of ACM, MTZ, and NMS during zebrafish's initial development.</p><p><strong>Methods: </strong>Zebrafish embryos 6-8 h post-fertilization (hpf) were exposed to different concentrations of ACM, MTZ, and NMS, separately, to obtain the 50% lethal concentrations (LC₅₀). Next, the embryos were exposed to distinct concentrations of the cocktail (LC₅₀/2, LC₅₀/5, LC₅₀/10, and LC₅₀/20) in a semi-static system. Samples were analyzed 0, 24, 48, and 96 h after exposure, and the drugs' concentrations in E3 medium were assessed by high-performance liquid chromatography. For embryotoxicity evaluation, the mortality, hatching, and heart rates; total length; and pericardial and yolk sac areas were determined. In addition, body malformations, edemas, presence of pigmentation, and histopathological assessments were also recorded.</p><p><strong>Results: </strong>The LC₅₀ values obtained for MTZ, ACM, and NMS were 4.69 mgmL^-1, 799.98 μgmL^-1, and 0.92 μgmL^-1, respectively. No difference was observed between the drugs' nominal and observed concentrations at each time point. The cocktail significantly induced mortality and decreased hatching in the LC₅₀/10, LC₅₀/5, and LC₅₀/2 groups. Additionally, body malformations, pigmentation loss, and yolk sac and pericardial edemas were observed in the cocktail groups. The cocktail groups' larvae had decreased total length and slower heart rates compared to the controls (p < 0.05). The histopathological assessment showed that yolk sac edema promoted severe histological changes in the esophageal-intestine junction and intestine in larvae treated with cocktails. Moreover, PAS-positive structures decreased in the esophageal-intestine junction, intestine, and liver in larvae exposed to pharmaceutical cocktails.</p><p><strong>Conclusion: </strong>This study's findings suggest the cocktail of ACM, MTZ, and NMS may be hazardous to aquatic organisms in case of environmental contamination.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"585-597"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579228","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":"Plausible mechanism of drug resistance and side-effects of COVID-19 therapeutics: a bottleneck for its eradication.","authors":"Swarnali Das, Sreyashi Nath, Shahjahan, Sanjay Kumar Dey","doi":"10.1007/s40199-024-00524-z","DOIUrl":"10.1007/s40199-024-00524-z","url":null,"abstract":"<p><strong>Background: </strong>COVID-19 pandemic has turned our world upside down by meddling with our normal lives. While there is no definitive drug against SARS-CoV-2, antiviral drugs that are already in the market, are being repurposed against it, could now complete long-term as well as all age-specific investigations, and they are successful in saving millions of lives. Nevertheless, side-effects are emergingly seen in the patients undergoing treatment, and ineffectiveness is increasingly found due to the emerging notorious variants of the virus. Many of them are also facing serious co-infections including black fungus, Zika, and H1N1 virus to name a few.</p><p><strong>Objectives: </strong>Therefore, this review highlights both drug resistance, their side-effects, and the significance for proper and long-term clinical trials of all age groups including children.</p><p><strong>Methods: </strong>We have explored and proposed the mechanisms of drug resistance that may arise due to the misuse or overuse of drugs based on available experimental reports.</p><p><strong>Results: </strong>The review provides solutions to the aforesaid issues of drug-resistance and side-effects by providing combination therapies, ancillary treatments, and other preventive strategies that can be useful in preventing drawbacks thereby curbing COVID-19 or similar future infections to maintain our normal lives.</p><p><strong>Conclusion: </strong>COVID-19 and its long-term effects, if any, can be eradicated with strategic and mindful use of related therapeutics in a controlled manner.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"801-823"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723276","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":"Targeting resistant breast cancer stem cells in a three-dimensional culture model with oleuropein encapsulated in methacrylated alginate microparticles.","authors":"Ozlem Altundag-Erdogan, Rumeysa Tutar, Elif Yüce, Betül Çelebi-Saltik","doi":"10.1007/s40199-024-00512-3","DOIUrl":"10.1007/s40199-024-00512-3","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Cancer stem cells (CSCs) are a subpopulation of cancer cells that are believed to be responsible for tumor initiation, progression, metastasis, and resistance to conventional therapies. Oleuropein as a natural compound found in olive leaves and olive oil, has potential therapeutic effects in cancer treatment, particularly in targeting CSCs. It induces apoptosis in CSCs while sparing normal cells, inhibit proliferation, migration, and invasion, and suppress the self-renewal ability of CSCs. Additionally, oleuropein has shown synergistic effects with conventional chemotherapy drugs, enhancing their efficacy against CSCs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;This study aims to selectively target therapeutically resistant cancer stem cells (CSCs) within a heterogeneous tumor population by utilizing oleuropein (OLE) encapsulated in methacrylated alginate (OLE-mALG) within an in vivo-like microenvironment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;This study aims to target therapeutically resistant cancer stem cells (CSCs) with oleuropein (OLE) encapsulated in the methacrylated alginate (OLE-mALG) in a heterogeneous tumor population with an in vivo-like microenvironment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Co-culture of CSCs with non-tumorogenic MCF-12 A cells was performed, the 3D breast cancer model was supported with methocel/matrigel/collagen-I, and vascularization was ensured with human umbilical vein endothelial cells (HUVEC). Then, OLE-loaded methacrylated alginate microparticles (mALG) were formed by dual crosslinking in the presence of both ionic and visible light obtained with a droplet based microfluidic system. The characterization and effectiveness of the produced OLE-mALG were evaluated by the FTIR, swelling/degradation/release analysis. Before producing OLE loaded mALG microparticles, a preliminary study was carried out to determine the effective dose of OLE for cells and the duration of OLE action on MCF-7, CSCs and MCF-12 A. Subsequently, CSC viability (WST-1), apoptosis (Bcl-2, Bax, caspase-3, caspase-9), stemness (OCT3/4, NANOG, SOX2), EMT profile (E-cadherin, Vimentin, Slug) and proliferation (SURVIVIN, p21, CYCLIN D1) after OLE-mALG treatment were all evaluated in the 3D model.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;OLE was encapsulated in mALG with an efficiency of 90.49% and released 73% within 7 h. OLE-mALG induced apoptosis through the decrease in anti-apoptotic Bcl-2 and an increase in pro-apoptotic Bax, caspase-3, and caspase-9 protein levels. While Vimentin and Slug protein levels decreased after 200 µg/mL OLE-mALG treatment to 3D breast cancer culture, E-cadherin levels increased. OLE-mALG treatment to CSC co-culture led to a decrease in proliferation by triggering p21/SURVIVIN expressions, and also resulted in an increase in stemness genes (OCT3/4/NANOG/SOX2).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;200 µg/mL OLE-loaded mALG microparticles suppressed epithelial-to-mesenchymal transition by suppressing Vimentin and Slug","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"471-483"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897265","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":"Pharmacogenetic DPYD allele variant frequencies: A comprehensive analysis across an ancestrally diverse Iranian population.","authors":"Negar Sarhangi, Fatemeh Rouhollah, Negar Niknam, Farshad Sharifi, Shekoufeh Nikfar, Bagher Larijani, George P Patrinos, Mandana Hasanzad","doi":"10.1007/s40199-024-00538-7","DOIUrl":"10.1007/s40199-024-00538-7","url":null,"abstract":"<p><strong>Background: </strong>Cancer treatment has improved over the past decades, but many cancer patients still experience adverse drug reactions (ADRs). Pharmacogenomics (PGx), known as personalized treatment, is a pillar of precision medicine that aims to optimize the efficacy and safety of medications by studying the germline variations. Germline variations in the DPYD lead to significant ADRs. The present cross-sectional study aims to evaluate the allele frequency of the DPYD gene variations in the Iranian population to provide insights into personalized treatment decisions in the Iranian population.</p><p><strong>Methods: </strong>The allele frequency of 51 pharmacogenetic variations in the clinically relevant DPYD was assessed in a representative sample set of 1142 unrelated Iranian individuals and subpopulations of different ethnic groups who were genotyped using the Infinium Global Screening Array-24 BeadChip.</p><p><strong>Results: </strong>The genotyping assay revealed eight pharmacogenetic variants including DPYD rs1801265 (c.85T > C; DPYD*9A), rs2297595 (c.496A > G), rs1801158 (c.1601G > A; DPYD*4), rs1801159 (c.1627A > G; DPYD*5), rs1801160 (c.2194G > A; DPYD*6), rs17376848 (c.1896T > C), rs56038477 (c.1236G > A; HapB3), and rs75017182 (c.1129-5923C > G; HapB3) with minor allele frequency (MAF) ≥ 1%.</p><p><strong>Conclusion: </strong>The results of the study reveal significant genetic variations among Iranian population that could significantly influence clinical decision-making. These variants, with their potential to explain the substantial variability in drug response phenotypes among different populations, shed light on a crucial aspect of pharmacogenomics. These findings not only provide valuable insights but also inspire the design and implementation of future pharmacogenomic clinical trials, motivating further research in this crucial area.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"715-727"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460026","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":"Public interest in drug-related problems reflected in information search trends: an infodemiological study.","authors":"Laura Martínez-Aguilar, María Sanz-Lorente, Fernando Martínez-Martínez, María J Faus, Javier Sanz-Valero","doi":"10.1007/s40199-024-00519-w","DOIUrl":"10.1007/s40199-024-00519-w","url":null,"abstract":"<p><strong>Background: </strong>The analysis of how people search and \"navigate\" the internet to obtain health-related information and how they communicate and share this information can provide valuable knowledge about the disease patterns behaviour and health habits of populations.</p><p><strong>Objective: </strong>To determine the population's interest in drug-related problems through information search trends.</p><p><strong>Method: </strong>A descriptive ecological correlational study, based on obtaining Google Trends data.</p><p><strong>Variables studied: </strong>relative search volume (RSV), evolution over time, milestones and seasonality.</p><p><strong>Results: </strong>The most searched topic was drug overdose, with mean RSV of 56.25 ± 0.65. The highest increase occurred in the contraindication topic (R² = 0.87, p < 0.001). The main milestone was observed in the drug overdose topic in July 2018 (RSV = 100). A very close relationship was found between adverse drug reaction and contraindication (R = 0.89, p < 0.001). Slight seasonality was noted in the adverse drug reaction (augmented Dickey-Fuller test [ADF] = -1.96), contraindication (ADF = -2.66) and drug interaction (ADF = -1.67) topics, but did not show an epidemiological trend.</p><p><strong>Conclusions: </strong>The greatest public interest was found in the drug overdose and contraindication topics, which showed a stronger upward trend, although the seasonality study did not show any very notable data or demonstrate epidemiological information search behaviour. The main milestone observed was due to media factors related to the consumption of narcotics. There was a clear difference in English-speaking countries in the use of the drug overdose topic. A correlation between the adverse drug reaction and contraindication topics was confirmed.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"537-547"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418206","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":"Population Pharmacokinetics of Loxoprofen and its alcoholic metabolites in healthy Korean men.","authors":"Ji-Hun Jang, Ho-Suk Kang, Seung-Hyun Jeong","doi":"10.1007/s40199-024-00533-y","DOIUrl":"10.1007/s40199-024-00533-y","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Loxoprofen has been actively used clinically to relieve musculoskeletal pain and inflammatory symptoms. However, there are few reports on quantitative pharmacokinetic (PK) prediction tools and diversity analyzes for loxoprofen within populations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;The aim of this study was to identify effective covariates associated with explaining inter-individual PK variability through a population pharmacokinetic (Pop-PK) modeling approach for loxoprofen, and to provide a starting point for establishing scientific dosing regimens.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Method: &lt;/strong&gt;The bioequivalence PK results of loxoprofen performed on 52 healthy Korean men and the physiological and biochemical parameters derived from each individual were used as base data for the development of a Pop-PK model of loxoprofen. In order to simultaneously predict the PKs of the active form according to loxoprofen exposure, previously reported PK results of trans-alcohol loxoprofen, an active metabolite of loxoprofen, were used to expand the model.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The Pop-PK profiles of loxoprofen were described in terms of the basic structure of a non-sequential two absorption with 2-disposition compartment, and for inter-individual PK variations, peripheral compartment volume of distribution could be correlated with body surface area (BSA), and central compartment clearance with creatinine clearance (CrCL) and albumin levels. As a result of the model simulation, the concentrations of loxoprofen and its alcoholic metabolites in plasma significantly decreased as CrCL and albumin levels increased and decreased, respectively. On the other hand, it was confirmed that the higher the BSA, the greater the distribution of loxoprofen to the periphery, and the minimum concentrations of loxoprofen and alcoholic metabolites in plasma in steady-state increased by approximately 1.78-2 times, while the fluctuation between maximum and minimum concentrations decreased. The results suggest that patients with large BSA, impaired renal function, and high serum albumin levels may have significantly higher plasma exposure to loxoprofen and trans-alcohol loxoprofen. It was also suggested that the potential side effects in the gastrointestinal system and various tissues and the level of exposure in plasma due to long-term application of loxoprofen in this patient group could be causally explained.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study provides a very useful starting point for a scientific precision medicine approach to loxoprofen by discovering effective covariates and establishing a quantitative model that can explain the diversity of loxoprofen PKs within the population.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Clinical trial registration: &lt;/strong&gt;The clinical study protocol used in this study was thoroughly reviewed and approved by the Institutional Review Board of the Institute of Bioequivalence and Bridging Study, Chonnam National University, Gwangju, Rep","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"631-648"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141981944","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":"Hybrid derivatives containing dimethyl fumarate and benzothiazole scaffolds for the potential treatment of multiple sclerosis; in silico & in vivo study.","authors":"Seyedeh Azin Mirmotahari, Mehdi Aliomrani, Farshid Hassanzadeh, Hajar Sirous, Mahboubeh Rostami","doi":"10.1007/s40199-024-00529-8","DOIUrl":"10.1007/s40199-024-00529-8","url":null,"abstract":"<p><strong>Background: </strong>Multiple Sclerosis (MS) is a chronic autoimmune, inflammatory neurological disease of the CNS. Riluzole and dimethyl fumarate (DMF) are two FDA-approved drugs to treat amyotrophic lateral sclerosis (ALS) and MS. Riluzole (a benzothiazole derivative) inhibits glutamate release from nerve terminals by antagonizing the N-Methyl-D-Aspartate (NMDA) receptor, and DMF upregulates anti-oxidative pathways.</p><p><strong>Objectives: </strong>Herein, using molecular hybridization strategy, we synthesized some new hybrid structures of Riluzole and DMF through some common successive synthetic pathways for evaluating their potential activity for remyelination in MS treatment.</p><p><strong>Methods: </strong>Molecular docking experiments assessed the binding affinity of proposed structures to the NMDA active site. The designed structures were synthesized and purified based on well-known chemical synthesis procedures. Afterward, in vivo evaluation for their activity was done in the C57Bl/6 Cuprizone-induced demyelination MS model.</p><p><strong>Results and conclusion: </strong>The proposed derivatives were recognized to be potent enough based on docking studies (ΔG_bind of all derivatives were -7.2 to -7.52 compare to the Ifenprodil (-6.98) and Riluzole (-4.42)). The correct structures of desired derivatives were confirmed using spectroscopic methods. Based on in vivo studies, D4 and D6 derivatives exhibited the best pharmacological results, although only D6 showed a statistically significant difference compared to the control. Also, for D4 and D6 derivatives, myelin staining confirmed reduced degeneration in the corpus callosum. Consequently, D4 and D6 derivatives are promising candidates for developing new NMDA antagonists with therapeutic value against MS disorders.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"599-615"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893074","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}