ADMET and DMPK最新文献

{"title":"Rapid detection of illegal selective androgen receptor modulators in unregistered supplements using a combination of selected solid-state analytical methods.","authors":"Izabela Jendrzejewska, Lubos Cehlarik, Tomasz Goryczka, Ewa Pietrasik, Natalia Pawlik, Josef Jampilek","doi":"10.5599/admet.2685","DOIUrl":"10.5599/admet.2685","url":null,"abstract":"<p><strong>Background and purpose: </strong>Pharmaceutical crime is becoming an increasingly serious threat. For customs officers and police officers, minimal or no sample preparation before analysis is essential when detecting prohibited compounds/counterfeit products, ideally using on-site analysis.</p><p><strong>Experimental approach: </strong>Unregistered dietary supplements containing anabolic substances, specifically selective androgen receptor modulators (SARMs) such as andarine, ligandrol, ostarine, and testolone became the subject of investigation. Dietary supplements with these SARMs are often found illegally in various fitness centres and can be purchased online. Furthermore, these illegal supplements may not contain the declared SARMs at all or may contain incorrect amounts. Analytical methods such as Raman spectroscopy, differential scanning calorimetry, thermogravimetry, and X-ray powder diffraction were chosen to identify these banned SARMs in the illegal products.</p><p><strong>Key results: </strong>Using a combination of these fast and direct analytical techniques, in particular, Raman spectroscopy, it was found that out of 16 samples, SARMs were confirmed in 9 samples, while no testolone (4 samples), ostarine (2 samples), or andarine (1 sample) was reliably identified in 7 samples.</p><p><strong>Conclusion: </strong>Overall, almost half of the analyzed samples of unregistered/illegal sports dietary supplements purchased anonymously online in the Slovak Republic with declared content of at least one SARM did not contain what is declared on the label. Thus the combination of several solid-state analytical techniques without complex sample preparation has proven valuable for rapid identification of APIs in supplements.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"13 3","pages":"2685"},"PeriodicalIF":3.4,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting bone in cancer therapy: Advances and challenges of bisphosphonate-based drug delivery systems.","authors":"Mohammadmahdi Eshaghi, Fariba Ganji, Hossein Shaki, Lobat Tayebi","doi":"10.5599/admet.2756","DOIUrl":"10.5599/admet.2756","url":null,"abstract":"<p><strong>Background and purpose: </strong>Bisphosphonates (BPs) are well-known for their strong affinity toward bone mineral matrices and are widely used to inhibit excessive osteoclast activity associated with various bone disorders. Beyond their clinical use, their unique bone-targeting capability has positioned them as promising ligands for drug delivery systems aimed at treating bone-related cancers.</p><p><strong>Approach: </strong>The review analyses published studies on BP-functionalized drug delivery systems, including direct drug conjugates, calcium-based nanomaterials, carbon-based nanostructures, and self-assembling systems such as micelles and liposomes. In vitro assays (<i>e.g.</i> hydroxyapatite binding, cell viability) and in vivo biodistribution studies are discussed to evaluate targeting efficiency and therapeutic outcomes. The impact of BP structure, linker chemistry, and carrier material on drug release and bone accumulation is examined.</p><p><strong>Key results: </strong>BP-functionalized systems consistently demonstrate improved bone targeting and enhanced drug accumulation at tumour sites compared to non-targeted approaches. Both direct conjugates and nanocarrier-based systems show promising results, with some formulations offering controlled drug release and reduced systemic toxicity. Despite these advances, certain challenges such as burst release and incomplete clinical validation remain.</p><p><strong>Conclusion: </strong>This review highlights the significant progress in BP-based drug delivery platforms for bone cancer therapy, demonstrating their potential to concentrate therapeutic agents at bone tumour sites while minimizing off-target effects. The integration of nanotechnology with BP targeting offers new opportunities for treating bone metastases and primary bone tumours. However, further research is needed to address current limitations and translate these findings into clinical practice.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"13 3","pages":"2756"},"PeriodicalIF":3.4,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging machine learning models in evaluating ADMET properties for drug discovery and development.","authors":"Magesh Venkataraman, Gopi Chand Rao, Jeevan Karthik Madavareddi, Srinivas Rao Maddi","doi":"10.5599/admet.2772","DOIUrl":"10.5599/admet.2772","url":null,"abstract":"<p><strong>Background and purpose: </strong>The evaluation of ADMET properties remains a critical bottleneck in drug discovery and development, contributing significantly to the high attrition rate of drug candidates. Traditional experimental approaches are often time-consuming, cost-intensive, and limited in scalability. This review aims to investigate how recent advances in machine learning (ML) models are revolutionizing ADMET prediction by enhancing accuracy, reducing experimental burden, and accelerating decision-making during early-stage drug development.</p><p><strong>Experimental approach: </strong>This article systematically examines the current landscape of ML applications in ADMET prediction, including the types of algorithms employed, common molecular descriptors and datasets used, and model development workflows. It also explores public databases, model evaluation metrics, and regulatory considerations relevant to computational toxicology. Emphasis is placed on supervised and deep learning techniques, model validation strategies, and the challenges of data imbalance and model interpretability.</p><p><strong>Key results: </strong>ML-based models have demonstrated significant promise in predicting key ADMET endpoints, outperforming some traditional quantitative structure - activity relationship (QSAR) models. These approaches provide rapid, cost-effective, and reproducible alternatives that integrate seamlessly with existing drug discovery pipelines. Case studies discussed in this review illustrate the successful deployment of ML models for solubility, permeability, metabolism, and toxicity predictions.</p><p><strong>Conclusion: </strong>Machine learning has emerged as a transformative tool in ADMET prediction, offering new opportunities for early risk assessment and compound prioritization. While challenges such as data quality, algorithm transparency, and regulatory acceptance persist, continued integration of ML with experimental pharmacology holds the potential to substantially improve drug development efficiency and reduce late-stage failures.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"13 3","pages":"2772"},"PeriodicalIF":5.1,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of surfactants and polymer composition on the characteristics of polyhydroxyalkanoate nanoparticles.","authors":"Aleksei Dorokhin, Sergei Lipaikin, Galina Ryltseva, Alexander Shabanov, Kristina Sapozhnikova, Tatiana Volova, Sergei Kachin, Ekaterina Shishatskaya","doi":"10.5599/admet.2723","DOIUrl":"10.5599/admet.2723","url":null,"abstract":"<p><strong>Background and purpose: </strong>Polyhydroxyalkanoates (PHAs) are biodegradable polyesters of bacterial origin that are actively studied as matrices for the preparation of nanoparticulate drug delivery systems. The most significant parameters affecting PHAs nanoparticles (NPs) characteristics are polymer composition and the type of surfactant used to stabilize the emulsion during NPs preparation. However, there are only a few studies in the literature investigating the effect of these factors on the characteristics of PHA NPs.</p><p><strong>Experimental approach: </strong>Blank poly(3-hydroxybutyrate) (P3HB) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (P3HBV) NPs were produced and characterized in terms of their size, morphology and zeta potential. Poly(vinyl alcohol) (PVA) with various molecular weights (31-50 and 85-124 kDa), as well as Tween 20 (TW20), Tween 80 (TW80), sodium deoxycholate (SDC) and sodium dodecyl sulphate (SDS) were used as surfactants. For NPs that formed stable aqueous suspensions and had the most desirable characteristics (P3HB/PVA_31-50 and P3HBV/PVA_31-50), hemolytic activity and cytotoxicity to HeLa and C2C12 cells in vitro were determined.</p><p><strong>Key results: </strong>NPs of both P3HB and P3HBV obtained using PVA with the <i>M</i> _w of 31-50 kDa as a surfactant had regular spherical shape, uniform size distribution, average diameter of about 900 nm and zeta potential of -28.5 and -28.7 mV, respectively. PVA_85-124, TW20 and TW80, as well as SDC and SDS as surfactants, did not show satisfactory results due to suspension gelation, formation of hollow NPs with irregular shape and poor resuspension after washing and freeze-drying, respectively. P3HB/PVA_31-50 and P3HBV/PVA_31-50 NPs did not have hemolytic activity and did not show pronounced cytotoxicity to HeLa and C2C12 cells in the concentration range from 10 to 500 μg mL^-1, so these samples were regarded as safe and biocompatible.</p><p><strong>Conclusion: </strong>In this study, the effect of various non-ionic and anionic surfactants on the characteristics of P3HB and P3HBV NPs was investigated. PVA_31-50 was found to be effective in producing NPs of both studied polymers with good biocompatibility and favorable characteristics, making them suitable for drug delivery applications. In contrast, other studied surfactants, <i>i.e.</i>, PVA_85-124, TW20, TW80, SDC and SDS, require further investigation. The obtained findings may promote the development of novel PHA-based nanomedicines.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"13 3","pages":"2723"},"PeriodicalIF":3.4,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epirubicin-sensitive detection with a CoWO₄/reduced graphene oxide modified screen-printed electrode.","authors":"Somayeh Tajik, Razieh Moghimian, Hadi Beitollahi","doi":"10.5599/admet.2733","DOIUrl":"10.5599/admet.2733","url":null,"abstract":"<p><strong>Background and purpose: </strong>Because of its antimetabolic and cytotoxic qualities, epirubicin (EP), a crucial chemotherapeutic drug, has been used to treat a number of cancers, including those of the prostate, breast, ovary, stomach, lung, and colon.</p><p><strong>Experimental approach: </strong>In this study, CoWO₄/reduced graphene oxide (CoWO₄/rGO) nanocomposite was synthesised and characterised by field emission-scanning electron microscopy and energy-dispersive X-ray spectroscopy. To provide a novel sensing platform for EP determination, a screen-printed electrode (SPE) surface was modified using the as-fabricated CoWO₄/rGO nanocomposite.</p><p><strong>Key results: </strong>Using voltammetric techniques, the electrochemical behaviour of the CoWO₄/rGO nanocomposite modified SPE (CoWO₄/rGO/SPE) for the EP detection was examined. CoWO₄/rGO significantly reduced the overpotential of the EP redox reaction and increased the rate of electron transfer between the electrode and analyte as compared to bare SPE. EP was quantitatively analysed using differential pulse voltammetry.</p><p><strong>Conclusions: </strong>It was discovered that the linearity range was 0.01 to 190.0 μM. The sensitivity and limit of detection were 0.1529 μA μM^-1 and 0.007 μM, respectively. Additionally, the constructed CoWO₄/rGO/SPE sensor's practical applicability was investigated in pharmaceutical samples with good recovery outcomes.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"13 3","pages":"2733"},"PeriodicalIF":3.4,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insight into antistaphylococcal effect of chlorinated 1-hydroxynaphthalene-2-carboxanilides.","authors":"Lucia Vrablova, Tomas Gonec, Petra Majerova, Andrej Kovac, Dominika Kos, Peter Kollar, Jiri Kos, Alois Cizek, Tereza Kauerova, Josef Jampilek","doi":"10.5599/admet.2684","DOIUrl":"https://doi.org/10.5599/admet.2684","url":null,"abstract":"<p><strong>Background and purpose: </strong>New compounds and innovative therapeutic approaches are trying to prevent antimicrobial resistance, which has become a global health challenge.</p><p><strong>Experimental approach: </strong>This study includes a series of twelve mono-, di- and trichlorinated 1-hydroxynaphthalene-2-carboxanilides designed as multitarget agents. All compounds were evaluated for their antistaphylococcal activity. Furthermore, MTT assay and chemoproteomic analysis of selected compounds were performed. Cytotoxicity in human cells was also tested.</p><p><strong>Key results: </strong><i>N</i>-(3,5-Dichlorophenyl)-1-hydroxynaphthalene-2-carboxamide (<b>10</b>) demonstrated activity comparable to or higher than clinically used drugs, with minimum inhibitory concentrations (MICs) of 0.37 μM. The compound was equally effective against clinical isolates of methicillin-resistant <i>S. aureus</i>. On the other hand, compound <b>10</b> showed 96 % inhibition of <i>S. aureus</i> respiration only at a concentration of 16× MIC. Chemoproteomic analysis revealed that the effect of agent <b>10</b> on staphylococci resulted in the downregulation of four proteins. This compound expressed no <i>in vitro</i> cytotoxicity up to a concentration of 30 μM.</p><p><strong>Conclusion: </strong>From the set of tested mono-, di- and trisubstituted derivatives, it is evident that the position of chlorine atoms is decisive for significant antistaphylococcal activity. Inhibition of energy metabolism does not appear to be one of the main mechanisms of action of compound <b>10</b>; on the contrary, the antibacterial effect may likely be contributed by downregulation of proteins (especially ATP-dependent protease ATPase subunit HslU) involved in processes essential for bacterial survival and growth, such as protein, nucleotide/nucleic acid synthesis and efficient protein repair/degradation.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"13 2","pages":"2684"},"PeriodicalIF":3.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12043106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin-loaded nanoemulsion for acute lung injury treatment <i>via</i> nebulization: Formulation, optimization and <i>in vivo</i> studies.","authors":"Prashant Anilkumar Singh, Rajendra Awasthi, Ramendra Pati Pandey, Santosh K Kar","doi":"10.5599/admet.2661","DOIUrl":"https://doi.org/10.5599/admet.2661","url":null,"abstract":"<p><strong>Introduction: </strong>Curcumin, a polyphenolic bioactive molecule, exhibits potent anti-inflammatory and antioxidant properties by reducing cytokine levels such as IL-6, TNF-α, and TGF-β. It regulates IL-17A and modulates key signaling pathways, including PI3K/AKT/mTOR, NF-κB and JAK/STAT. However, its clinical application is hindered by rapid metabolism, poor solubility, and chemical instability.</p><p><strong>Method: </strong>Using the Box-Behnken design, this study developed and optimized a curcumin-loaded turmeric oil-based nanoemulsion system. The effects of turmeric oil, Tween 80 and sonication cycles on particle size (PS), polydispersity index (PDI), and encapsulation efficiency were analyzed. The optimized nanoemulsion was characterized by zeta potential, PDI, PS, morphology, loading efficiency, EE, and antioxidant activity (DPPH assay). <i>In vitro</i> cytotoxicity was evaluated using A549 cells, while <i>in vivo</i> efficacy was assessed in BALB/c mice through histological analysis, bronchoalveolar lavage fluid analysis, and TNF-α and IL-1β estimation via enzyme-linked immunosorbent assay.</p><p><strong>Results: </strong>The optimized nanoemulsion had high entrapment efficiency (92.45±2.4 %), a PS of 130.6 nm, a PDI of 0.151, and a zeta potential of -1.7±0.6 mV. Nanoparticle tracking analysis confirmed a mean PS of 138.3±1.6 nm with a concentration of 3.78×10¹² particles/mL. Transmission electron microscopy imaging confirmed spherical morphology. The <i>IC</i> ₅₀ value was 25.65 μg/mL. The nanoemulsion remained stable for three months at 4±1 and 25±2 °C/ 60±5 % relative humidity. The optimized formulation significantly reduced BALF total cell count, alveolar wall thickening, and TNF-α and IL-1β levels (<i>p</i> < 0.001).</p><p><strong>Conclusion: </strong>Overall, the optimized formulation significantly lowered levels of pro-inflammatory cytokines in the acute lung injury /acute respiratory distress syndrome mouse model.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"13 2","pages":"2661"},"PeriodicalIF":3.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12043102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chitosan-modified ceftazidime loaded polyhydroxyalkanoates microparticles: preparation, characterization and antibacterial evaluation <i>in vitro</i>.","authors":"Anastasiya Murueva, Natalia Zhila, Alexey Dudaev, Ekaterina Shishatskaya, Tatiana Volova","doi":"10.5599/admet.2645","DOIUrl":"https://doi.org/10.5599/admet.2645","url":null,"abstract":"<p><strong>Background and purpose: </strong>The use of drug delivery systems to enhance the efficacy of existing antimicrobial drugs is one of the promising approaches to combat bacterial resistance. The simultaneous presence of a polycationic biopolymer (chitosan) and an antibacterial drug (ceftazidime) in polyhydroxyalkanoates microparticles is more effective since it allows such carriers to have a more pronounced therapeutic effect. In this study, chitosan-modified ceftazidime-loaded poly(3-hydroxybutyrate-3-hydroxyvalerate-3-hydroxyhexanoate) (P(3HB-3HV-3HHх)) microparticles were prepared and investigated as a drug delivery system.</p><p><strong>Experimental approach: </strong>The obtained microparticles were characterized in terms of their particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency, drug release studies <i>in vitro</i>, cytotoxicity and antibacterial properties in cell cultures.</p><p><strong>Key results: </strong>The microparticles had spherical shapes with diameters from 0.6 to 1.6 μm. The constructed chitosan-modified ceftazidime-loaded microparticles are a depot form of drug, the release of which <i>in vitro</i> is realized for a long time, without burst releases, corresponds to Korsmeyer-Peppas and Higuchi models. <i>In vitro</i> cell viability and proliferation studies on designed microparticles investigated using HaCaT (human keratinocyte skin cell lines) showed good cell proliferation. The hemolytic activity of chitosan-modified P(3HB- 3HV-3HHх) microparticles evaluated by hemolysis assay demonstrated good blood compatibility. Chitosan-modified microparticles enhanced the antibacterial activity of ceftazidime, being effective against <i>E. coli</i> and <i>St. aureus</i>.</p><p><strong>Conclusion: </strong>Thus, the obtained drug delivery systems based on PHAs and chitosan in the form of microparticles can be promising means in treating infectious skin diseases for topical use.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"13 2","pages":"2645"},"PeriodicalIF":3.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12043104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical pharmacokinetics, distribution, metabolism and excretion of disitamab vedotin.","authors":"Ling Wang, Limeng Zhu, Fengzhu Wang, Lihou Dong, Zhihao Liu, Fang Chen, Jing Jiang","doi":"10.5599/admet.2582","DOIUrl":"https://doi.org/10.5599/admet.2582","url":null,"abstract":"<p><strong>Background and purpose: </strong>Disitamab vedotin is an antibody-drug conjugate (ADC) composed of a humanized IgG1 monoclonal antibody (mAb) targeting HER2 conjugated to monomethyl auristatin E(MMAE) via a cleavable dipeptide linker.</p><p><strong>Experimental approach: </strong>The pharmacokinetics, distribution, catabolism/metabolism and elimination properties of disitamab vedotin and its payload MMAE were characterized in rats and tumour-bearing mice.</p><p><strong>Key results: </strong>The configured mAb and total antibody showed linear dynamic characteristics. Moreover, the molecular structure of disitamab vedotin effectively reduces the exposure of MMAE, which has a fast clearance. Two radiolabeled probes were developed to track the fate of different components of the disitamab vedotin, including ¹²⁵I labelled antibody and ³H labelled MMAE payload of the ADC. Following a single intravenous administration of the radiolabeled probes to the tumour-bearing mice and rats, blood, various tissues, and excreta samples were collected and analyzed for radioactivity and to characterize the metabolites/catabolites. Disitamab vedotin and free MMAE (FM) were majorly distributed in tissues and organs with rich blood flow. Moreover, both disitamab vedotin and MMAE have higher and longer exposure in tumour tissue. Disitamab vedotin was mainly eliminated through renal excretion, while the FM was mainly eliminated through the biliary faecal route (>70 %) and a small fraction (<10 %) was eliminated through renal excretion in the form of catabolites/metabolites, among which, MMAE was identified as the major species, along with 10 other minor species.</p><p><strong>Conclusion: </strong>These studies provided significant insight into disitamab vedotin pharmacokinetics, distribution, metabolism and elimination properties, which supports the clinical development of disitamab vedotin.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"13 2","pages":"2582"},"PeriodicalIF":3.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12043107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two-dimensional Co-based metal-organic framework nanosheets as an efficient electrochemical sensing platform for simultaneous determination of daunorubicin and idarubicin.","authors":"Somayeh Tajik, Erfan Beiromi, Hadi Beitollahi, Fariba Garkani Nejad, Zahra Dourandish","doi":"10.5599/admet.2686","DOIUrl":"https://doi.org/10.5599/admet.2686","url":null,"abstract":"<p><strong>Background and purpose: </strong>Chemotherapy is the most effective and commonly utilized cancer treatment method. Therefore, studies on the sensitive determination of chemotherapy drugs used in cancer treatment can be very effective in improving treatment and reducing their side effects.</p><p><strong>Experimental approach: </strong>The two-dimensional Co-based metal-organic framework nanosheets (2D Co-MOF NSs) were synthesized and then utilized to modify the screen-printed carbon electrode (2D Co-MOF NSs/SPCE). The 2D Co-MOF NSs/SPCE was successfully used for the determination of daunorubicin (DNR). Furthermore, we utilized differential pulse voltammetry, cyclic voltammetry, and chronoamperometry to evaluate the electrochemical properties of the created electrode.</p><p><strong>Key results: </strong>The obtained results from CV studies demonstrate that this sensor exhibits outstanding electrocatalytic activity for the redox process of DNR. Under optimal experimental conditions, quantitative measurements resulted in a linear concentration range from 0.004 to 450.0 μM for DNR with a limit of detection (LOD) of 0.001 μM. Furthermore, the fabricated electrode was used for the simultaneous voltammetric detection of DNR and idarubicin (IDR). According to the results, the 2D Co-MOF NSs/SPCE sensor showed two well-defined peaks for the voltammetric oxidation of DNR and IDR. Eventually, the practical sample detection of DNR and IDR was successfully validated with acceptable results.</p><p><strong>Conclusion: </strong>The developed sensing platform will be beneficial for enabling effective medical strategies to improve the clinical efficacy of chemotherapy drugs.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"13 2","pages":"2686"},"PeriodicalIF":3.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12043108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}