Tiago Sousa , Conor Beaupres De Monsales , Charlotte Yeung , Anders Borde , Bertil Abrahamsson , Abdul W. Basit
{"title":"Evaluating rat and canine microbiota models for predicting human colonic prodrug metabolism","authors":"Tiago Sousa , Conor Beaupres De Monsales , Charlotte Yeung , Anders Borde , Bertil Abrahamsson , Abdul W. Basit","doi":"10.1016/j.ejps.2025.107273","DOIUrl":"10.1016/j.ejps.2025.107273","url":null,"abstract":"<div><div>The rise of microbiome-aware drug development has placed growing emphasis on the need for reliable preclinical tools to evaluate microbiota-mediated drug metabolism. While human faecal models are used, they suffer from practical limitations such as donor recruitment and regulatory constraints. Larger animals like dogs are often assumed to be more translationally relevant yet are resource-intensive and subject to more complex regulatory and logistical requirements. Rats offer a more accessible, cost-effective and scalable alternative. However, it remains unclear whether their faecal material alone accurately reflects colonic metabolism. Specifically, it is unknown whether faecal samples capture the same metabolic activity as more invasive caecal or colonic contents, or how closely they reflect drug degradation in larger animal models or humans. This study aimed to: (i) compare degradation of three prodrugs across Wistar rat faecal, caecal, and colonic compartments; (ii) determine how rat degradation profiles differ from those observed in Labradors; and (iii) evaluate how closely rat and canine data align with published human in vitro results. Degradation kinetics of sulfasalazine, balsalazide, and olsalazine were first assessed. Bioreactors prepared from 10% faecal, caecal, and colonic contents in rats were used. Faecal material showed equivalent metabolic activity to colonic and caecal material across all drugs (two-way ANOVA, p = 0.233), with sulfasalazine degrading most rapidly (t₁/₂ = 29.1 min), followed by balsalazide (t₁/₂ = 47.9 min), and olsalazine (t₁/₂ = 84.1 min). These findings indicate that faecal material can reliably substitute for more invasive gut content sampling, offering practical and procedural advantages. Subsequent interspecies comparisons revealed that rats exhibited significantly higher degradation rates than dogs (P < 0.05), reflecting known differences in gut microbial density and composition. When benchmarked against published human in vitro data, rat degradation rates were closely aligned with human values, particularly for sulfasalazine (rat: <em>K</em> = 0.025 min⁻¹; human: <em>K</em> = 0.021 min⁻¹) and balsalazide (rat: <em>K</em> = 0.015 min⁻¹; human: <em>K</em> = 0.009 min⁻¹). These findings highlight rat faecal material as a practical and translationally relevant model for microbiota-sensitive prodrug metabolism, offering a low-impact alternative to invasive sampling and larger animal studies.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107273"},"PeriodicalIF":4.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080012","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}
Maryana Salamah , Bence Sipos , Gábor Katona , Balázs Volk , György Tibor Balogh , Ildikó Csóka
{"title":"Development and validation of a novel isocratic RP-HPLC method using AQbD approach for the quantification of favipiravir","authors":"Maryana Salamah , Bence Sipos , Gábor Katona , Balázs Volk , György Tibor Balogh , Ildikó Csóka","doi":"10.1016/j.ejps.2025.107276","DOIUrl":"10.1016/j.ejps.2025.107276","url":null,"abstract":"<div><h3>Background/Objectives</h3><div>In this study, the analytical quality by design (AQbD) approach was used to develop an eco-friendly reversed-phase high-performance liquid chromatography (RP–HPLC) method to identify and quantify favipiravir (FAV).</div></div><div><h3>Methods</h3><div>A risk assessment identified factors significantly impacting method performance. Three high level risk factors (X1: ratio of solvent, X2: pH of the buffer, X3: column type) were selected to study their impact on the following output responses: peak area (Y1), retention time (Y2), tailing factor (Y3) and theoretical plates count (Y4) using <span>d</span>-optimal experimental design. The method operable design region (MODR) and the robust set point were calculated using a Monte Carlo simulation method using the MODDE® 13 Pro software.</div></div><div><h3>Results</h3><div>The method was developed using an Inertsil® ODS-3 C18 column (250 mm, 4.6 mm, 5 μm, and 100 Å). The mobile phase was composed of A: acetonitrile and B: disodium hydrogen phosphate anhydrous buffer (pH 3.1, 20 mM) in a 18:82 v/v ratio, and was eluted at an isocratic-flow-rate of 1 mL/min at 30 °C with DAD detection at 323 nm. The method was validated as per the USP and ICH guidelines. The system suitability test parameters were within the USP limits. The method showed excellent linearity, sensitivity and selectivity. The optimized method showed good precision, accuracy and robustness with RSD value 〈 2 %. Additionally, the developed RP-HPLC method based AQbD approach showed excellent Analytical Eco-Scale score 〉 75, and was successfully applied for quantify FAV in the laboratory- prepared tablets.</div></div><div><h3>Conclusions</h3><div>AQbD is a useful tool to replace existing traditional methods for the optimization of a green, validated RP-HPLC method, for the routine analysis and quality control of FAV.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107276"},"PeriodicalIF":4.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079973","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}
Min Yuan , Xin Lin , Haolun Ding , Sicheng Qu , Yaning Yang , Xu Steven Xu
{"title":"Treatment-agnostic joint modeling of longitudinal circulating tumor dna predicts survival across first-line regimens in metastatic non-squamous NSCLC","authors":"Min Yuan , Xin Lin , Haolun Ding , Sicheng Qu , Yaning Yang , Xu Steven Xu","doi":"10.1016/j.ejps.2025.107275","DOIUrl":"10.1016/j.ejps.2025.107275","url":null,"abstract":"<div><h3>Background and Purpose</h3><div>To develop a treatment-agnostic joint model leveraging longitudinal circulating tumor DNA (ctDNA) dynamics to predict overall survival (OS) across different treatment regimens without incorporating treatment information using data from the IMpower150 trial in treatment-naïve metastatic non-squamous NSCLC patients.</div></div><div><h3>Experimental approach</h3><div>Patients were randomized 1:1:1 to receive ABCP, ACP, or BCP, with plasma samples collected at baseline and multiple time points to track longitudinal ctDNA changes. The joint model followed a two-step approach by combining two separate submodels: a disease submodel for ctDNA dynamics and a survival submodel for time-to-event analysis. Random effects are derived from the nonlinear mixed effects model for ctDNA dynamics. In the subsequent step, these individual random effects are incorporated as covariates in the survival submodel. A landmark modeling approach was used where ctDNA data from the first 21 weeks posttreatment was used to predicts OS beyond 21 weeks.</div></div><div><h3>Key Results</h3><div>Among 466 participants, 348 had detectable ctDNA at one or more time points and were stratified into training (<em>n</em> = 181) and test (<em>n</em> = 167) sets. Fourteen ctDNA summary metrics were assessed, with median allele frequency for known/likely mutations emerging as the top-performing metric. Overall, the treatment-agnostic model's predicted survival curves closely matched the observed ones across treatment arms in both training and test sets. Predicted median OS and 2-/3-year OS rates aligned well for ABCP, ACP, and BCP, with discrepancies generally under 20 %. Although the model tended to overpredict OS for ACP—likely due to a small sample size—the final IMpower150 analysis reported median OS values within 10 % of our predictions.</div></div><div><h3>Conclusions & Implications</h3><div>Early ctDNA monitoring and modeling have the potential to significantly enhance treatment personalization. By enabling the early prediction of patient outcomes across various treatment regimens, this treatment-agnostic model supports more informed clinical decision-making, ultimately improving patient management and outcomes in oncology.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107275"},"PeriodicalIF":4.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080035","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-performance liquid chromatography method for simultaneous determination of the degradation products of metformin hydrochloride and vildagliptin","authors":"Amra Demirović , Alija Uzunović , Anisa Veledar-Hamalukić","doi":"10.1016/j.ejps.2025.107268","DOIUrl":"10.1016/j.ejps.2025.107268","url":null,"abstract":"<div><div>With the growing production of tablets containing two or more active pharmaceutical ingredients, analytical methods must align with this patient-friendly trend. The development and optimization of a gradient HPLC method for the simultaneous determination of degradation products of metformin and vildagliptin are performed using Full Factorial Design, which allows the significance check of selected factors. Central Composite Design optimizes the method to achieve the desired resolution between critical peak pairs.</div><div>During the optimization process, the pH and salt concentration in the buffer solution were adjusted, while the oven temperature remained unchanged compared to the initial chromatographic conditions. Separation was achieved using a reversed-phase column. Optimization improved the resolutions between all four critical peak pairs, especially for the critical pair related to vildagliptin. The response surface graphs were used to identify optimal experimental conditions, aligning fully with the optimized method. The aim of this paper is to present the method development and prove that it suits the intended purpose.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107268"},"PeriodicalIF":4.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063474","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":"Time shift in ciclosporin metabolism downregulation by inflammation in allogeneic hematopoietic cell transplantation: A time-dependent transduction modelling PK-PD approach","authors":"David Malnoë , Tony Marchand , Pascal Le Corre","doi":"10.1016/j.ejps.2025.107271","DOIUrl":"10.1016/j.ejps.2025.107271","url":null,"abstract":"<div><div>Ciclosporin is a major immunosuppressant in allogeneic hematopoietic stem cell transplantation (HSCT), with a narrow therapeutic index and high interindividual variability. We previously showed that severe inflammation significantly reduces cytochrome P450 3A4 (CYP3A4)-mediated ciclosporin metabolism, as reflected by an increased concentration-to-dose (C/D) ratio. However, the temporal dynamics between inflammation and ciclosporin metabolism remain poorly understood. This study aimed to characterize the time-dependent effect of inflammation—quantified by C-reactive protein (CRP) levels—on CYP3A4-mediated ciclosporin metabolism using a signal transduction pharmacokinetic-pharmacodynamic (PK-PD) modeling approach in HSCT patients. We selected 10 HSCT patients with a single moderate-to-severe inflammatory episode (CRP > 40 mg/L) and modeled CRP kinetics alongside ciclosporin C/D ratios using a transduction model. Key parameters included the maximum effect (E<sub>max</sub>), the CRP concentration at 50% of E<sub>max</sub> (EC<sub>50</sub>), and the time delay (τ) between CRP and metabolism variations. External validation was performed using published time profiles from Chen et al. 1994 and 2 patients with potential drug–drug interactions (pDDI) involving letermovir from our cohort. The model captured a 4.7-fold increase in C/D ratio at an EC<sub>50</sub> of 120 mg/L of CRP, with a time delay of 6 days between CRP peak and C/D ratio peak. External validation confirmed strong predictive performance. In patients with moderate-to-severe inflammation, inflammation-driven CYP3A4 downregulation appeared to outweigh the impact of letermovir-mediated DDI. Our results provide the first quantitative evidence of time-dependent inhibition due to inflammation of ciclosporin metabolism. This quantitative modeling framework may inform dose adjustment and DDI risk evaluation in inflammatory conditions, particularly in allogeneic HSCT patients.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107271"},"PeriodicalIF":4.7,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058496","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":"Tailoring polyethersulfone membranes with polycitrate for controlled transdermal delivery of azithromycin to enhance therapeutic potential","authors":"Mahya Samari , Soheila Kashanian , Sirus Zinadini , Hossein Derakhshankhah","doi":"10.1016/j.ejps.2025.107263","DOIUrl":"10.1016/j.ejps.2025.107263","url":null,"abstract":"<div><div>This study explores the development and application of polycitrate-modified membranes for controlled drug delivery. The synthesis of polycitrate was achieved through the self-condensation of citric acid, confirmed by FT-IR spectroscopy, which indicated successful polymerization. Scanning electron microscopy revealed a two-layered membrane structure with a dense top-layer and porous sub-layers. The incorporation of polycitrate increased porosity (from 39.48 % to 64.81 %) and hydrophilicity, enhancing pore formation and drug release. Membranes with 1.5 wt. % polycitrate (M4) showed the best performance, achieving a release of 455 mg/L of azithromycin, with a zero-order release mechanism ensuring a steady rate. The optimal membrane thickness for drug release efficiency was found to be 300 µm, effectively balancing storage capacity with release characteristics. Evaluations confirmed the membranes' reusability and stability through 10 cyclic loading and sterilization processes. The increased water vapor transmission rates indicated their suitability as wound dressings, promoting an optimal healing environment. Additionally, improvements in tensile strength and controlled degradation highlight the potential of these membranes for advanced drug delivery systems. Overall, polycitrate-modified membranes emerge as a promising solution for transdermal drug delivery in clinical applications.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107263"},"PeriodicalIF":4.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052433","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}
Farnaz Shokraneh , Anne M. Filppula , Aleksi Tornio , Jaan Aruväli , Urve Paaver , Ivan Kassamakov , Niklas Sandler Topelius
{"title":"Automated 3D printing of pediatric furosemide tablets: A personalized medicine approach using semi-solid extrusion and NIR monitoring","authors":"Farnaz Shokraneh , Anne M. Filppula , Aleksi Tornio , Jaan Aruväli , Urve Paaver , Ivan Kassamakov , Niklas Sandler Topelius","doi":"10.1016/j.ejps.2025.107269","DOIUrl":"10.1016/j.ejps.2025.107269","url":null,"abstract":"<div><div>This study presents the development of personalized, immediate-release furosemide tablets for pediatric use using semi-solid extrusion (SSE) 3D printing integrated with compounding system solution (CSS) technology. Dose personalization and real-time quality assurance were implemented using near-infrared (NIR) spectroscopy with partial least squares (PLS) modeling, supported by Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and surface characterization via scanning white light interferometry (SWLI).</div><div>Furosemide formulations (1 % and 2 % w/w) were prepared using a gel-based excipient and printed in doses from 2 to 10 mg. The NIR-based PLS model exhibited strong predictive accuracy (R² = 0.91; RMSEC = 3.37 %), enabling effective, non-destructive blend uniformity monitoring. All formulations met European Pharmacopoeia requirements for drug content (85.0–115.0 %) and content uniformity (AV < 15). Dissolution testing confirmed rapid release profiles, with >85 % release for all freshly prepared tablets. After six months, the 2 % formulation retained adequate performance (88.5 %), while the 1 % formulation showed a moderate decline (76.3 %).</div><div>FTIR and XRD analyses revealed no significant drug–excipient interactions, and the crystalline structure of furosemide remained intact throughout storage. SWLI demonstrated surface morphology variations between formulations, revealing that excipient and surfactant levels influenced microtopography and potentially drug release kinetics.</div><div>The integration of SSE 3D printing with spectroscopic and imaging tools offers a robust, reproducible, and patient-centric platform for personalized pediatric drug manufacturing. This approach supports the transition toward automated, non-sterile compounding with real-time control, improved dose precision, and enhanced product quality—addressing long-standing gaps in pediatric pharmaceutical care.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107269"},"PeriodicalIF":4.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052404","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}
Laura Victoria Schulte-Werning , Ivo Laidmäe , Lisa Myrseth Hemmingsen , Jyrki Heinämäki , Liis Preem , Karin Kogermann , Ann Mari Holsæter
{"title":"Antimicrobial core-shell nanofiber wound dressing with chloramphenicol-liposomes","authors":"Laura Victoria Schulte-Werning , Ivo Laidmäe , Lisa Myrseth Hemmingsen , Jyrki Heinämäki , Liis Preem , Karin Kogermann , Ann Mari Holsæter","doi":"10.1016/j.ejps.2025.107264","DOIUrl":"10.1016/j.ejps.2025.107264","url":null,"abstract":"<div><div>In the context of a rising incidence of chronic wounds worldwide, developing more efficient wound dressings is in demand. In this setting, nanofiber dressings have shown promising features. We combined three biopolymers: beta-glucan (βG), chitosan (CHI) and pectin into the same nanofibers. In addition, antimicrobial activity was provided adding chloramphenicol (CAM), which also was entrapped in liposomes for a more sustained drug release. Applying a coaxial electrospinning setup allowed fabricating core-shell nanofibers, with βG and CHI in the shell, and pectin with CAM liposomes in the core. Initially, challenges during electrospinning with gel-clogging of the needle tip emerged, due to the formation of a polyelectrolyte complex between the positively charged CHI and negatively charged pectin. This happened although pectin and CHI were separated in the coaxial electrospinning setup. Here, the critical intervention to solve this problem was reducing the pH of the pectin-containing core-solution. The successful electrospun core-shell nanofibers (Coax-LipCAM), with a mean diameter of around 200 nm, was confirmed by SEM and TEM images. Among the control nanofibers, a mono-axial control-nanofiber, Mono-core-CAM, was prepared. This control formulation contained the same polymers as present in the core of the Coax-LipCAM together with “free” CAM (not entrapped in liposomes). When Mono-core-CAM was compared with Coax-LipCAM, Coax-LipCAM exhibited enhanced tensile strength and higher stability in simulated wound fluid. Furthermore, CAM release from Coax-LipCAM was extended, with 80 % of the drug released after eight hours. Finally, all CAM-containing nanofibers showed antimicrobial activity comparable to pure CAM when tested against <em>Escherichia coli</em> and <em>S. aureus</em>. In conclusion, core-shell nanofibers with CAM-liposomes in a pectin-core and with a shell contained βG and CHI, were successfully prepared. Their promising morphological and mechanical characteristics, favorable stability and swelling properties, sustained CAM release, and preserved antimicrobial activity encourages further clinical evaluation targeting the treatment of chronic wounds.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107264"},"PeriodicalIF":4.7,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039432","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}
Jessica A. Dominguez Rieg , Monika Domenech Acevedo , Jennifer Nogueira Coelho , Monica Stevens , Linto Thomas , Timo Rieg
{"title":"Distinct roles of ferric carboxymaltose and ferric derisomaltose on phosphate homeostasis in iron deficiency anemia","authors":"Jessica A. Dominguez Rieg , Monika Domenech Acevedo , Jennifer Nogueira Coelho , Monica Stevens , Linto Thomas , Timo Rieg","doi":"10.1016/j.ejps.2025.107265","DOIUrl":"10.1016/j.ejps.2025.107265","url":null,"abstract":"<div><div>Intravenous (IV) iron-carbohydrate nanoparticles like ferric carboxymaltose (FCM) and ferric derisomaltose (FDI) are used to treat iron deficiency anemia (IDA); however, they differ in their side-effects (e.g., hypophosphatemia). We compared the effects of FCM and FDI in a newly generated mouse model of IDA and determine their efficacy in resolving IDA and effects on mineral homeostasis. Eight-week-old female C57Bl/6J mice were fed an iron-deficient diet for 5 weeks followed by IV bleeding (0.7 % of body weight) for 3 consecutive days to establish IDA. On day 1 and 7 after induction of IDA, mice were injected with vehicle, FCM or FDI (both 20 mg kg<sup>-1</sup>). On day 14, blood, urine and tissues were collected. Compared to baseline, all mice developed microcytic hypochromic anemia. FCM and FDI treatment resolved IDA, reversed thrombocytosis, and prevented the development splenomegaly and cardiomegaly observed in vehicle-treated anemic mice. Plasma iron increased to a greater extent with FCM versus FDI. Plasma iron showed an inverse relationship with intact fibroblast growth factor 23 (iFGF23) and C-terminal FGF23 (cFGF23). The ratio of iFGF23:cFGF23 increased in all groups but for different reasons: vehicle (iFGF23↑, cFGF23↔); FCM and FDI (iFGF23↔, cFGF23↓). The ratio was ∼1.8-fold greater in FDI versus FCM at the end of the experimental period. Only FCM caused hypophosphatemia, despite the abundance of the renal Na<sup>+</sup>-P<sub>i</sub> cotransporter 2a being similarly lower (∼30 % versus vehicle) with FDI. Our results demonstrate that while FCM and FDI are equally effective at resolving IDA, hypophosphatemia is not solely caused by renal mechanisms.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107265"},"PeriodicalIF":4.7,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039453","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}