European Journal of Pharmaceutical Sciences最新文献

{"title":"Preclinical safety assessment of holmium-based microspheres for micro-brachytherapy in mice","authors":"Nienke Johanna Maria Klaassen ,&nbsp;Milou Boswinkel ,&nbsp;Nino Chiron Morsink ,&nbsp;Alexandra Gil Arranja ,&nbsp;Guillaume Cornelis Maria Grinwis ,&nbsp;Janneke Molkenboer-Kuenen ,&nbsp;Jan Willem Hesselink ,&nbsp;Sebastiaan Alexander van Nimwegen ,&nbsp;Johannes Frank Wilhelmus Nijsen","doi":"10.1016/j.ejps.2025.107419","DOIUrl":"10.1016/j.ejps.2025.107419","url":null,"abstract":"<div><h3>Introduction</h3><div>Holmium-166 microspheres are suitable for micro-brachytherapy for various solid tumours, due to their favourable characteristics regarding treatment and imaging. The purpose of this study was to investigate acute- to long-term toxicity, 3 days to 12 months, biodegradation and <em>in vivo</em> holmium release of two types of holmium-based microspheres, containing poly(L-lactic acid) (Ho-PLLA-MS) or hydroxide (Ho-(OH)₃−MS), homogeneously suspended in an injection fluid comprised by colloidal microcrystalline cellulose (MCC) and phosphate buffer in healthy mice.</div></div><div><h3>Methods</h3><div>250 mice were included in the study. Non-radioactive holmium-165 microsphere suspensions, were injected subcutaneously on the flank of 150 mice, animals were intensively monitored. CT imaging was performed to visualise the location of the injection site, the distribution of the microspheres and the injection fluid and their possible translocation. Injection site and other relevant tissues were assessed histologically and possible holmium leakage or microsphere migration was examined by analysing the holmium content in the injection site and relevant tissues via inductively coupled plasma analysis (ICP).</div></div><div><h3>Results</h3><div>The injection of holmium-165 microspheres suspended in MCC-based injection fluid caused local inflammation ranging from slight to severe. No relevant deviations in haematological or biochemical parameters indicative for acute or chronic systemic toxicity were observed. ICP analysis and CT imaging showed no signs of microsphere translocation from the injection site to other organs.</div></div><div><h3>Conclusion</h3><div>These findings indicate that the injection fluid (MCC in phosphate buffer) in combination with Ho-(OH)₃−MS or Ho-PLLA-MS can potentially be used as administration fluid for controlled localized microsphere delivery. However, prior to clinical application, clinically relevant doses have to be tested in sensitive anatomical regions.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107419"},"PeriodicalIF":4.7,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145793553","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":"1,3,5-Triazine-benzenesulfonamide hybrids: are they cytotoxic?","authors":"Mária Bodnár Mikulová ,&nbsp;Jana Hricovíniová ,&nbsp;Michal Hanko ,&nbsp;Gabriela Greifová","doi":"10.1016/j.ejps.2025.107416","DOIUrl":"10.1016/j.ejps.2025.107416","url":null,"abstract":"<div><div>In contemporary pharmaceutical research, cytotoxicity assays constitute an indispensable tool in the systematic evaluation of drug candidates. The identification of cytotoxic effects at early stages of development is critical, as it allows for the elimination of compounds with unfavourable toxicological properties prior to their advancement into preclinical and clinical testing. Despite the essential role of cytotoxicity studies, the relationship between chemical structure and cytotoxic outcome remains insufficiently defined for many classes of compounds. In this context, 1,3,5-triazine derivatives have emerged as a particularly promising scaffold due to their broad spectrum of biological activities, with notable emphasis on anticancer potential. However, the absence of a comprehensive structure–cytotoxicity correlation highlights the need for systematic evaluation and consolidation of findings. In this review, we provide an overview of triazine-benzenesulfonamide hybrid molecules, including their synthesis and purification procedures, as well as their biological activity and cytotoxicity. The novel strategies in new candidate drug development and structure modifications related to their effects on investigated protein and/or non-protein targets, as well as various cell lines, are included to demonstrate a relationship between structure and antiproliferative activity, as well as cytotoxicity. Moreover, the literature reveals substantial variability in the methods used to assess antiproliferative and cytotoxic activity, which hinders comparisons and the interpretation of structure–activity relationships. Adoption of a standardized framework—particularly consistent reporting of IC₅₀ values—would improve reproducibility, facilitate meaningful cross-study comparisons, and provide a stronger foundation for linking molecular design with biological response. Ultimately, such standardisation may advance drug discovery and support the rational modification of chemical structures to enhance therapeutic potential.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107416"},"PeriodicalIF":4.7,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773876","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":"A novel microbubble delivery platform with high payload of paclitaxel upon focused ultrasound for enhanced glioblastoma treatment","authors":"Yudie Yan ,&nbsp;Kihwan Hwang ,&nbsp;Jungmin Lee ,&nbsp;Kyung Mi Nam ,&nbsp;Soyeon Shin ,&nbsp;Been Yoon ,&nbsp;Zhen Zhang ,&nbsp;Myoung-Hwan Park ,&nbsp;Chae-Yong Kim","doi":"10.1016/j.ejps.2025.107415","DOIUrl":"10.1016/j.ejps.2025.107415","url":null,"abstract":"<div><div>Effective chemotherapy for glioblastoma (GBM) is severely limited by the impermeability of the blood-brain barrier (BBB). Although paclitaxel (PTX) demonstrates potent anti-glioma activity <em>in vitro</em>, its poor BBB penetration precludes its clinical use for GBM. We developed a novel PTX-loaded microbubble (PTX@MB) platform designed for targeted drug delivery to gliomas via low-intensity focused ultrasound (LIFU). PTX@MB were fabricated using a perfluorocarbon (PFC) liquid core stabilized by F-127, and their physicochemical properties were characterized. <em>In vitro</em> anti-tumor effects were evaluated using U87MG cells in both 2D culture and 3D spheroid models. For <em>in vivo</em> assessment, an orthotopic U87MG glioma mouse model was utilized. Following intravenous administration of PTX@MB, LIFU was applied to the tumor region to induce localized drug release and transient BBB disruption. Therapeutic outcomes were evaluated by MRI, survival analysis, and histopathology. The fabricated PTX@MB were spherical, with a high drug encapsulation efficiency of 89.1 ± 0.5 %, and exhibited ultrasound-responsive drug release. <em>In vitro</em>, the combination of PTX@MB and ultrasound exposure demonstrated dose-dependent cytotoxicity and significant inhibition of U87MG spheroid growth. In the orthotopic mouse model, the PTX@MB + LIFU treatment significantly suppressed tumor progression and prolonged median survival compared to the control group. The PTX@MB + LIFU system significantly reduced tumor burden without notable systemic toxicity. This ultrasound-responsive platform enables targeted PTX delivery across the BBB and offers a promising, non-invasive strategy for site-specific chemotherapy in neuro-oncology.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107415"},"PeriodicalIF":4.7,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145755745","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":"Early prediction of tablet defects during pan coating","authors":"Joona Sorjonen ,&nbsp;Luis Martin de Juan ,&nbsp;Pirjo Tajarobi ,&nbsp;Håkan Wikström ,&nbsp;Jarkko Ketolainen","doi":"10.1016/j.ejps.2025.107414","DOIUrl":"10.1016/j.ejps.2025.107414","url":null,"abstract":"<div><div>The appearance of a tablet is a critical quality attribute that can be directly evaluated by patients. During tablet manufacturing, mechanical stress may lead to visual defects, such as edge chipping, the prediction of which remains a major challenge, particularly during technology transfer or scale-up processes. This study aimed to evaluate whether the number and severity of defects could be predicted under two mechanical stress environments: pan coating and friabilator testing.</div><div>A breakage model was calibrated using drop tests with two placebo formulations: mannitol:microcrystalline cellulose (7:3) and microcrystalline cellulose:anhydrous dibasic calcium phosphate (7:3), both at target tensile strengths of 1.5–2.5 MPa. Discrete element method (DEM) simulations were used to estimate the collision velocities and frequencies in the coating pan, enabling defect prediction using the breakage model. One verification run was performed using the mannitol:MCC 7:3 formulation at 2.0 MPa, which was also used to predict the tablet appearance in the friabilator.</div><div>The model accurately predicted the severity of defects (Classes I–III, where I is the least and III the most severe defect) in the coating trial but underestimated the number of Class I defects. The numerical predictions made by the model are exponentially affected by inaccuracies in the calibration of model parameters, particularly for small damage. Visual differences between tablets with equal mass loss in the friabilator and pan coater also suggest that wear from low-force collisions contributed to damage during the coating process. In contrast, the number of appearance defects was overpredicted in the friabilator, highlighting the model’s limitations in systems with frequent collisions. Overall, with careful calibration and under conditions with few defect-causing events, the model can provide useful guidance for defect prediction.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107414"},"PeriodicalIF":4.7,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145755167","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":"Recent developments of novel nanotechnology-based drug delivery systems for dermal and transdermal applications","authors":"Nazlı Erdoğar ,&nbsp;Betül Gür ,&nbsp;Dilara Örgül","doi":"10.1016/j.ejps.2025.107413","DOIUrl":"10.1016/j.ejps.2025.107413","url":null,"abstract":"<div><div>Topical and transdermal drug delivery faces continuous challenges, primarily due to the formidable barrier function of the stratum corneum (SC), which limits the bioavailability of therapeutics. Nanotechnology-based drug delivery systems (NDDS) have emerged as powerful strategies to overcome these limitations, offering improved drug permeation, sustained release, and enhanced solubility for hydrophobic compounds. This review provides a critical and concise analysis of the latest advancements in NDDS, specifically those employed for both dermal (localized) and transdermal (systemic) delivery. Key nanosystems, including lipid-based, polymeric nanoparticles, vesicular structures, nanoemulsions, nanofibers, dendrimers and micelles are explored, highlighting how their unique physicochemical properties facilitate optimized drug performance. Crucially, the design strategies that selectively target the dermis versus those engineered for transdermal penetration are compared and contrasted. Furthermore, the often-overlooked clinical aspects, including the current understanding of the in vivo fate, biocompatibility, and safety profile of these nanocarriers within the skin layers, are addressed. This comprehensive evaluation provides a foundation for future development of safer and more effective nanomedicines for cutaneous applications.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107413"},"PeriodicalIF":4.7,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751765","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":"Elucidating the roles of TM7SF3 and LHFPL6 in the putative H+/OC antiporter function in the human brain capillary endothelial cell line, hCMEC/D3","authors":"Nana Svane ,&nbsp;Toshiki Kurosawa ,&nbsp;Benjamin Schmid ,&nbsp;Lasse Saaby ,&nbsp;Mie Kristensen ,&nbsp;Hidetsugu Tabata ,&nbsp;Yoshiyuki Kubo ,&nbsp;Tetsuya Terasaki ,&nbsp;Birger Brodin ,&nbsp;Yoshiharu Deguchi","doi":"10.1016/j.ejps.2025.107409","DOIUrl":"10.1016/j.ejps.2025.107409","url":null,"abstract":"<div><h3>Introduction</h3><div>The putative proton/organic cation (H⁺/OC) antiporter has been shown to mediate transport of CNS drug compounds like oxycodone and pyrilamine across the blood-brain barrier (BBB). This transporter has a broad substrate profile and is able to transport substrates against their concentration gradient, making it an interesting target for brain drug delivery. However, the molecular identity of this transporter remains unknown. Recent studies have indicated that the two proteins TM7SF3 and LHFPL6 might be components of this transporter. The present study aimed to investigate the roles of TM7SF3 and LHFPL6 in the H⁺/OC antiporter function to advance understanding of its molecular identity and potential in CNS drug delivery.</div></div><div><h3>Methods</h3><div>CRISPR-Cas9 gene-editing was used to generate three hCMEC/D3 knockout (KO) cell lines: TM7SF3 KO (TM-KO), LHFPL6 KO (LH-KO), and a double KO of TM7SF3 and LHFPL6 (TMLH-KO). The uptake of pyrilamine analogue (EDMPG) and [³H]-pyrilamine was assessed in wild type (WT) and KO lines. Quantitative Realtime Polymerase Chain Reaction (qRT-PCR) confirmed successful gene knockouts. Passive diffusion properties and the expression and functionality of known BBB transporters, including LAT1 (<em>SLC7A5</em>), GLUT1 (<em>SLC2A1</em>), and MCT1 (<em>SLC16A1</em>), were also examined.</div></div><div><h3>Results</h3><div>The EDMPG uptake was significantly reduced in TM-, LH-, and TMLH-KO cells, suggesting that TM7SF3 and LHFPL6 contribute to the H⁺/OC antiporter function. However, [³H]-pyrilamine uptake remained unchanged across all KOs, indicating a TM7SF3- and LHFPL6-independent transport mechanism. This was further supported by the persistent inhibition of [³H]-pyrilamine uptake in the presence of known H⁺/OC antiporter substrates. While passive diffusion and GLUT1- and MCT1-mediated transport were unaffected, LAT1-mediated uptake of [³H]L-leucine and gabapentin (Neurontin) was significantly reduced in LH- and TMLH-KO cells, correlating with decreased LAT1 mRNA expression in these cells.</div></div><div><h3>Conclusions</h3><div>This study suggests that the <em>H</em>+/OC antiporter operates via two distinct mechanisms: a high-capacity, TM7SF3- and LHFPL6-independent pathway and a low-capacity, TM7SF3- and LHFPL6-dependent pathway. These findings underscore the complexity of the H⁺/OC antiporter molecular composition and highlight the need for further research to fully elucidate its identity.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107409"},"PeriodicalIF":4.7,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741596","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":"Advancing therapeutics with targeted formulations of hydrogen sulphide donors","authors":"Mandeep Kaur Marwah ,&nbsp;Lissette Sanchez-Aranguren ,&nbsp;Hala Shokr ,&nbsp;Mohamad Anas Al Tahan ,&nbsp;Keqing Wang ,&nbsp;Shakil Ahmad","doi":"10.1016/j.ejps.2025.107408","DOIUrl":"10.1016/j.ejps.2025.107408","url":null,"abstract":"<div><div>Hydrogen sulphide (H₂S), is a well described essential physiological molecule that is finely balanced to maintain cellular functions. Considering its important biological roles, H₂S has promising therapeutic potential resulting in the development of many H₂S donors. Such donors have proved to have therapeutic benefit in cognitive pathways, inflammation, reproduction, and the regulation of blood pressure. However, controlled delivery and targeted administration of this reactive and hazardous gas are necessary yet challenging due to its rapid diffusivity, and toxicity at high doses. Drug delivery systems are vital for the effective administration of many active pharmaceutical excipients, and H₂S donors stands to benefit significantly from the tuneable physical, chemical, and pharmacokinetic properties of various formulation systems. To date, few studies have focused on the formulation and delivery aspects of H₂S and its donors. Instead, H₂S usually is administered either by inhalation or via site-specific injections of donor solution. Whilst therapeutic benefit has been observed following such administration, these are not patient friendly solutions. This review focuses on highlighting the advances in H₂S donor formulations and their ability in sustaining the release of H₂S as well as improving drug targeting.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107408"},"PeriodicalIF":4.7,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145735723","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":"Single-dose pharmacokinetics of sublingual semaglutide in rats","authors":"Yi Liu ,&nbsp;Guiyun Song ,&nbsp;Daniel Banov ,&nbsp;Jennifer Denison ,&nbsp;Courtaney Davis ,&nbsp;Kendice Ip","doi":"10.1016/j.ejps.2025.107406","DOIUrl":"10.1016/j.ejps.2025.107406","url":null,"abstract":"<div><div>This study aims to compare the single-dose pharmacokinetic profiles of semaglutide administered via sublingual, oral, and injectable routes in Sprague–Dawley rats. Semaglutide was delivered sublingually in a proprietary anhydrous suspension vehicle. Rats were randomized into five groups and received the following treatments: subcutaneous injection (0.011 mg/kg), sublingual suspension (1 mg/kg, prepared from either commercial tablets or peptide powder), and oral tablets (1 mg/kg and 20 mg/kg). Semaglutide was detectable in plasma within 2 minutes post-dosing in all groups except the oral 1 mg/kg group. Sublingual administration demonstrated lower variability in plasma concentrations compared to oral dosing. At 1 mg/kg, the sublingual route achieved a significantly higher area under the curve (AUC) than oral (82.53 <em>vs.</em>15.08 ng*h/ml, <em>p</em>=0.004), indicating improved bioavailability. The maximum plasma concentration (C_max) was reached within 30 minutes for oral and sublingual routes, and at 8 hours for subcutaneous injection. The relative bioavailability was 0.06% for oral 1 mg/kg, 0.16% for oral 20 mg/kg, and 0.34% and 0.29% for sublingual 1 mg/kg using tablets or powder, respectively. No significant difference in AUC was observed between sublingual semaglutide prepared from oral tablets <em>versus</em> powder. These results highlight the potential of sublingual delivery of semaglutide and suggest this route may improve absorption while reducing variability. This proof-of-concept study supports further development of sublingual semaglutide formulations and pharmacokinetics research in humans.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107406"},"PeriodicalIF":4.7,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145735623","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":"Individualized dosing strategies in breast cancer chemotherapy: Evidence for therapeutic drug monitoring-guided docetaxel treatment","authors":"Ya-Min Liu ,&nbsp;Wei Huang ,&nbsp;Yong-Zhe Tang ,&nbsp;Hai Zhang ,&nbsp;Sheng-Ying Qin ,&nbsp;Jin Zhang ,&nbsp;Jun-Wei Fan ,&nbsp;Rui-Zhuo Ouyang ,&nbsp;Hai-Ou Yang ,&nbsp;Xiao-Qing Zhang","doi":"10.1016/j.ejps.2025.107407","DOIUrl":"10.1016/j.ejps.2025.107407","url":null,"abstract":"<div><h3>Background</h3><div>Docetaxel is a first-line chemotherapy drug for breast cancer and is traditionally dosed based on body surface area (BSA). However, this method often leads to significant inter-patient variability and a high incidence of adverse drug reactions (ADRs). Therapeutic drug monitoring (TDM) offers a personalized dosing approach that may improve drug safety and efficacy. This study aimed to evaluate the clinical and pharmacoeconomic benefits of TDM-guided dosing compared to traditional BSA-based dosing in breast cancer patients receiving docetaxel-based chemotherapy.</div></div><div><h3>Methods</h3><div>A randomized controlled study was conducted at the Department of Breast Surgery, IPMCH, from October 2022 to July 2024. A total of 208 breast cancer patients were enrolled and randomly assigned to two groups: the BSA group (<em>n</em> = 104) and the TDM-guided pharmacokinetics (PK) group (<em>n</em> = 104). Adverse drug reactions—including hematological, gastrointestinal, skin, neurotoxic, and cardiotoxic events—were monitored and compared between groups. Liver function markers (ALT, AST, ALP) and pharmacoeconomic data (treatment-related costs) were also assessed. Statistical analyses included univariate and interaction models to evaluate the impact of dosing strategy on ADRs and costs.</div></div><div><h3>Results</h3><div>Patients in the TDM-guided PK group exhibited significantly lower levels of ALT, AST, and ALP, indicating reduced hepatic toxicity. Gastrointestinal ADRs—including nausea, diarrhea, and constipation—were less frequent and less severe in the PK group compared to the BSA group. Overall, the incidence and severity of ADRs were markedly reduced in the PK group. Pharmacoeconomic analysis demonstrated consistently lower treatment-related costs in the PK group. Both univariate and interaction analyses confirmed the clinical and economic benefits of TDM-guided dosing.</div></div><div><h3>Conclusion</h3><div>TDM-guided docetaxel dosing significantly reduced ADRs and improved cost efficiency in breast cancer chemotherapy. These findings support the implementation of TDM as a superior strategy to traditional BSA-based dosing, with potential to enhance both patient safety and healthcare resource utilization.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107407"},"PeriodicalIF":4.7,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741614","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":"Pharmacokinetic profile of dexamethasone in urine and plasma after single and multiple oral administration: Relevance to doping controls","authors":"Sergi Coll ,&nbsp;Claudia Bressan ,&nbsp;Núria Monfort ,&nbsp;Ana Aldea-Perona ,&nbsp;Marcel·lí Carbó ,&nbsp;Rosa Ventura","doi":"10.1016/j.ejps.2025.107405","DOIUrl":"10.1016/j.ejps.2025.107405","url":null,"abstract":"<div><div>Dexamethasone (DEX) is prohibited in sports competitions when administered by all injectable, oral or rectal routes, and is permitted at all times when administered by all other routes. The present work aimed to assess the urinary excretion profile of DEX after single and multiple oral administrations to verify the suitability of the new minimum reporting level (MRL) of 60 ng/mL established by the World Anti-Doping Agency to distinguish allowed and prohibited administrations. Moreover, the minimum washout period of three days established for out-of-competition treatments with oral glucocorticoids will be evaluated.</div><div>DEX was administered to healthy volunteers using two different oral treatments: single administration (4 mg, <em>n</em> = 8 male volunteers) and multiple administrations (2 mg/12 h for 5 days, <em>n</em> = 8 male volunteers). Urine and plasma samples collected before and after administration were analysed using liquid chromatography-tandem mass spectrometry. DEX and 6β‑hydroxy-DEX, were the predominant compounds detected in urine, with peak urinary excretion observed within the first 4 h post-dose. DEX concentrations exceeded the new MRL mainly within 12 h after a single dose, with one volunteer showing levels above this threshold up to 24–36 h. In the multiple-dose study, most of the DEX concentrations remained above 60 ng/mL after the second dose and throughout the dosing period and declined quickly after the final dose. Plasma DEX kinetics was defined by an open bicompartmental model with a first order oral absorption. DEX was detectable up to 48 h post-administration. In the multiple dose study, the steady-state concentrations were reached soon after the first dose, and DEX showed no evidence of accumulation. CORT levels decreased rapidly after both single and multiple administrations due to suppression of the hypothalamic-pituitary-adrenal axis. Recovery times varied among volunteers.</div><div>The MRL of 60 ng/mL proved appropriate for distinguishing permitted from prohibited use with a 3-day washout, though further studies on non-systemic routes are recommended to refine sensitivity.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107405"},"PeriodicalIF":4.7,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145721647","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}