ADMET and DMPK最新文献

{"title":"Mortality prediction with adjuvant tamoxifen in breast cancer: Machine learning-integrated explainable artificial intelligence and Bayesian model results.","authors":"Kannan Sridharan, Gowri Sivaramakrishnan","doi":"10.5599/admet.3321","DOIUrl":"https://doi.org/10.5599/admet.3321","url":null,"abstract":"<p><strong>Background and purpose: </strong>Tamoxifen is a cornerstone of adjuvant endocrine therapy for breast cancer, yet significant inter-individual variability in treatment response and mortality exists. Identifying robust predictors of outcomes remains a critical need. This study integrated machine learning, explainable artificial intelligence (XAI) and Bayesian modelling to predict mortality and identify key prognostic factors in breast cancer patients receiving adjuvant tamoxifen.</p><p><strong>Experimental approach: </strong>We analysed data from 568 patients from the International Tamoxifen Pharmacogenomics Consortium database. The outcome was all-cause mortality, with predictors including age, race, menopausal status, tumour size, estrogen receptor status, radiation treatment, and CYP2D6 metabolizer status. Four algorithms, logistic regression, random forest, eXtreme Gradient Boosting (XGBoost) and support vector machine, were developed and validated. Model performance was assessed using accuracy and area under the receiver operating characteristic curve (AUC). SHapley Additive exPlanations (SHAP) analysis provided interpretability for the XGBoost model, and Bayesian logistic regression with weakly informative priors was employed for probabilistic inference.</p><p><strong>Key results: </strong>The overall mortality rate was 19.4 %. XGBoost demonstrated the highest discriminative ability (AUC 0.833; 95 % confidence interval: 0.725 to 0.941), while random forest exhibited superior sensitivity for identifying deceased patients (83.3 %). SHAP analysis revealed that white race, increased age, absence of radiation treatment, larger tumour size and the CYP2D6 poor metabolizer (PM/PM) genotype were associated with elevated mortality risk, whereas the extensive metabolizer (EM/EM) genotype was protective. Significant variability was observed in exploratory subgroup analyses, with the model achieving excellent discrimination in patients without radiation treatment (AUC 0.901) and those with the EM/PM genotype (AUC 0.956) but failing to identify any mortality events in the Caucasian subgroup. Bayesian logistic regression yielded comparable performance to frequentist methods (AUC 0.820), with tumour size emerging as a consistently strong predictor in partial dependence plots.</p><p><strong>Conclusion: </strong>Integrating machine learning with XAI and Bayesian approaches effectively identified key predictors of mortality in tamoxifen-treated breast cancer patients. However, marked heterogeneity in model performance across subgroups highlights the critical need for external validation and careful evaluation of algorithmic fairness before clinical implementation.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"14 ","pages":"3321"},"PeriodicalIF":4.3,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832310","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":"Linking biomimetic binding measurements to pharmacokinetic models of volume of distribution and hepatic clearance.","authors":"Klara Valko","doi":"10.5599/admet.3311","DOIUrl":"https://doi.org/10.5599/admet.3311","url":null,"abstract":"<p><strong>Background and purpose: </strong>The steady-state volume of distribution reflects the extent to which drugs partition between plasma and tissues and is closely related to the tissue-to-plasma partition coefficient. In pharmacokinetics, different modelling frameworks have led to ongoing debate regarding the role of plasma protein binding and the importance of unbound drug exposure in determining both distribution and clearance. This review aims to clarify the relationship between distribution and elimination models and to assess how experimental binding measurements can support their mechanistic interpretation.</p><p><strong>Experimental approach: </strong>Established pharmacokinetic relationships linking volume of distribution (<i>V</i> _d), clearance and half-life were analysed alongside biomimetic chromatographic measurements of drug binding to human serum albumin and phospholipid membranes using immobilized artificial membrane (IAM) chromatography. Literature data for marketed drugs were evaluated to examine how these experimental descriptors relate to distribution and clearance behaviour.</p><p><strong>Key results: </strong>The analysis shows that distribution and clearance models describe complementary aspects of drug disposition rather than contradictory processes. Tissue binding, as reflected by phospholipid affinity measured by IAM chromatography, plays a dominant role in determining <i>V</i> _d, while plasma protein binding influences both distribution and clearance through its effect on the fraction of drug unbound in plasma. The apparent paradox of plasma protein binding arises because changes in unbound fraction affect both processes simultaneously.</p><p><strong>Conclusion: </strong>This work demonstrates that biomimetic binding measurements provide a mechanistically meaningful bridge between physicochemical properties and pharmacokinetic behaviour. By integrating experimental binding data with pharmacokinetic models, the study advances understanding of how distribution and clearance are linked, supporting more informed decision-making in early drug discovery while highlighting that clearance remains influenced by additional factors beyond non-specific binding.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"14 ","pages":"3311"},"PeriodicalIF":4.3,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832301","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":"Simultaneous quantification of drug and coformer during cocrystal dissolution using <i>in situ</i> UV spectroscopy and multicomponent analysis.","authors":"Shiori Ishida, Samuel Lee, Balint Sinko, Karl Box, Kiyohiko Sugano","doi":"10.5599/admet.3274","DOIUrl":"https://doi.org/10.5599/admet.3274","url":null,"abstract":"<p><strong>Background and purpose: </strong>The primary objective of this study was to assess the feasibility of applying <i>in situ</i> UV spectroscopy in combination with multicomponent analysis (MCA) to simultaneously quantify the dissolution of a drug and its coformer from a cocrystal. A secondary objective was to determine whether this approach can support a mechanistic understanding of cocrystal dissolution.</p><p><strong>Experimental approach: </strong>The rotating-vessel μDISS system equipped with an <i>in situ</i> UV probe was used for dissolution tests. Carbamazepine (CBZ) cocrystals with saccharin, nicotinamide, and 2,4-dihydroxybenzoic acid were used as model compounds. The concentrations of CBZ and each coformer were simultaneously quantified using MCA of the <i>in situ</i> UV spectra.</p><p><strong>Key results: </strong>The concentrations of CBZ and the coformer were successfully quantified by MCA throughout the dissolution process. In the absence of a polymeric precipitation inhibitor (PPI), the dissolution of CBZ from the cocrystal reached only 20%, and no supersaturation was observed, whereas the coformers were rapidly released. In contrast, in the presence of PPIs, the dissolution of CBZ from the cocrystal increased to supersaturated levels, while the dissolution of the coformer decreased. Supersaturation of CBZ was achieved when CBZ and the coformer dissolved congruently. A PPI may interfere with the molecular dissociation of CBZ and the coformer from the cocrystal surface, resulting in a slower release of both CBZ and the coformer. This effect may have reduced the local CBZ concentration at the particle surface and, consequently, slowed the precipitation of CBZ dihydrate on the particle surface.</p><p><strong>Conclusion: </strong>MCA enables the simultaneous quantification of a drug and its coformer from <i>in situ</i> UV spectra during cocrystal dissolution testing. This analytical approach provides valuable insights into the dissolution mechanisms of cocrystals.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"14 ","pages":"3274"},"PeriodicalIF":4.3,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832252","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":"High-sensitivity electrochemical immunosensor for anti-SARS-CoV-2 IgG detection using screen-printed carbon/cerium oxide-gold electrode.","authors":"Melania Janisha Devi, Ratu Shifa Syafira, Shabarni Gaffar, Irkham Irkham, Yasuaki Einaga, Yeni Wahyuni Hartati","doi":"10.5599/admet.3182","DOIUrl":"https://doi.org/10.5599/admet.3182","url":null,"abstract":"<p><strong>Background and purpose: </strong>Serological assays are essential for evaluating immune responses, including donor screening, vaccine efficacy, and antibody persistence. However, conventional methods are time-consuming and require centralized laboratories. This study aimed to develop a sensitive and rapid electrochemical immunosensor based on a cerium oxide-gold nanocomposite (CeO₂-Au) modified screen-printed carbon electrode (SPCE) for the detection of anti-SARS-CoV-2 IgG, while elucidating the underlying electrochemical sensing mechanism.</p><p><strong>Experimental approach: </strong>CeO₂-Au nanocomposites were synthesized and characterized using UV-Vis, SEM, TEM-EDX, and FTIR. The immunosensor was fabricated by immobilizing SARS-CoV-2 Spike receptor-binding domain (RBD) onto the modified SPCE. Electrochemical responses were evaluated using differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) with K₃[Fe(CN)₆] as a redox probe.</p><p><strong>Key results: </strong>The CeO₂-Au nanocomposite enhanced electron transfer and provided a high surface area for biomolecule immobilization. The sensing mechanism is governed by modulation of interfacial electron transfer: binding of IgG to immobilized RBD forms an insulating immunocomplex layer, increasing charge transfer resistance and suppressing faradaic current. The sensor exhibited a wide linear range of 0.01 to 10³ ng mL^-1, a low detection limit of 2.475 pg mL^-1, good stability, and reliable 97.3 to 108.56 % recovery in serum samples.</p><p><strong>Conclusion: </strong>This immunosensor proposed as a sensitive and reliable platform for IgG detection. The study advances understanding of signal transduction mechanisms in nanocomposite-based immunosensors and highlights their potential for rapid serological diagnostics. However, broader clinical validation and selectivity against complex interferents remain necessary.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"14 ","pages":"3182"},"PeriodicalIF":4.3,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832212","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":"Potential of extracellular vesicles from human Wharton's jelly and golden berries (<i>Physalis peruviana</i>) combined with polyvinyl alcohol/chitosan/fibroin hydrogel for wound healing: <i>In vitro</i> approaches on 1BR3 cell line.","authors":"Afrida Rizky Nurfajrin, Indra Wibowo, Anggraini Barlian","doi":"10.5599/admet.3238","DOIUrl":"https://doi.org/10.5599/admet.3238","url":null,"abstract":"<p><strong>Background and purpose: </strong>The development of biocompatible delivery systems capable of enhancing wound healing remains a major challenge in drug delivery and regenerative medicine. Hydrogels represent promising wound dressings due to their ability to maintain a moist microenvironment, absorb exudates, and enable controlled release of bioactive agents. Recently, plant-derived exosome-like nanoparticles have emerged as a novel, non-toxic, and cross-kingdom therapeutic modality.</p><p><strong>Experimental approach: </strong>In this study, we investigated polyvinyl alcohol/chitosan/fibroin-based hydrogels as a delivery platform for plant-derived exosome-like nanoparticles isolated from <i>Physalis peruviana</i>, with human Wharton's jelly mesenchymal stem cell-derived exosomes used as a biological comparator.</p><p><strong>Key results: </strong>plant-derived exosome-like nanoparticles isolated from <i>Physalis peruviana</i> and human Wharton's jelly mesenchymal stem cell-derived exosomes were isolated and characterized in terms of size, morphology, and protein content. Composite hydrogels containing chitosan, polyvinyl alcohol, and fibroin (4 % and 10 %) were fabricated via freeze-thawing and characterized for hydrophilicity, swelling behaviour, water content, biodegradability, and protein release profiles. The biological performance of hydrogel-released media incorporating plant-derived exosome-like nanoparticles or human Wharton's jelly mesenchymal stem cell-derived exosomes was evaluated <i>in vitro</i> using human dermal fibroblast 1BR3 cells through cytotoxicity, proliferation, and scratch migration assays. The fabricated hydrogels exhibited hydrophilic surfaces (contact angle < 90°), high swelling capacity (> 100 %), low water content, and gradual biodegradation over 10 days. Protein release peaked on day 3, indicating favourable release kinetics for bioactive delivery. All hydrogel formulations demonstrated good biocompatibility, with cell viability exceeding 75 %. Notably, hydrogels loaded with plant-derived exosome-like nanoparticles isolated from <i>Physalis peruviana</i> significantly promoted fibroblast proliferation and migration, with performance comparable to or exceeding that of human Wharton's jelly mesenchymal stem cell-derived exosomes-loaded hydrogels, particularly in fibroin-containing formulations.</p><p><strong>Conclusion: </strong>These findings highlight the potential of <i>Physalis peruviana</i>-derived plant-derived exosome-like nanoparticles as a novel bioactive agent for wound healing and demonstrate that polyvinyl alcohol/chitosan/fibroin hydrogels serve as an effective delivery platform to enhance their biological activity. This study supports the translational potential of plant-derived exosome-like nanoparticles-based hydrogel systems for future wound healing applications.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"14 ","pages":"3238"},"PeriodicalIF":4.3,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832276","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":"Graphene-supported Pd/Pt nano-catalysts for enhanced colorimetric detection of dopamine and NADH using paper-based microfluidic devices.","authors":"Ruri Agung Wahyuono, Jovin Jovin, Ignacius Gilbert Chano, Arda Fridua Putra, Annisa Septyana Ningrum, Muhammad Yusuf Hakim Widianto, Irkham Irkham, Yeni Wahyuni Hartati, Wulan Tri Wahyuni, Isnaini Rahmawati, Chi-Hsien Huang, Yi-Ting Lai","doi":"10.5599/admet.3247","DOIUrl":"https://doi.org/10.5599/admet.3247","url":null,"abstract":"<p><strong>Background and purpose: </strong>Dopamine and nicotinamide adenine dinucleotide (NADH) are key biomarkers associated with neurological and metabolic disorders. Developing rapid, low-cost, and portable detection platforms of these biomarkers is essential for a point-of-care diagnostic kit. In this work, we report a colorimetric sensing approach using paper-based microfluidic devices (μPADs) modified with graphene-supported palladium (G/Pd) and platinum (G/Pt) nanocatalysts to enhance detection performance.</p><p><strong>Experimental approach: </strong>Monolayer G/Pd and G/Pt nanocomposites were synthesized via a hydrothermal method with precursor concentrations ranging from 0.1 to 10 mM. The catalytic behaviour and metal-graphene interactions were further investigated using spin-polarized density functional theory (DFT) calculation (PHASE/0). Microfluidic paper-based analytical devices (μPADs) were laser-printed on commercial filter paper and folded into 3D origami structures. Colorimetric responses were quantified using red, green, blue (RGB) and hue, saturation, value (HSV) analysis, where time-dependent Euclidean distance in RGB colour space was used to assess the reaction kinetics.</p><p><strong>Key results: </strong>DFT results indicate that Pd and Pt clusters preferentially adopt a top-site configuration on graphene, facilitating interfacial charge redistribution and enhancing catalytic activity experimentally. Catalyst-modified μPADs significantly improve reaction kinetics, reducing detection time by up to 3.7× for dopamine and 2.5× for NADH compared to unmodified devices. G/Pt (10 mM) exhibits the best overall performance, achieving limits of detection of 0.16 μM for dopamine and 0.195 μM for NADH with good linearity (<i>R</i> ² = 0.91). G/Pd displays competitive sensitivity, particularly at lower precursor concentration.</p><p><strong>Conclusion: </strong>The findings highlight that optimizing catalyst morphology and interfacial electronic structure is more critical than minimizing activation energy for achieving high-performance colorimetric sensing. The resulting platform shows potential as a cost-effective and portable tool for the detection of clinically relevant biomarkers in point-of-care settings.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"14 ","pages":"3247"},"PeriodicalIF":4.3,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832215","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":"Plantain peel extract-mediated synthesis of CuO nanoparticles: comprehensive characterization, bioinertness <i>in vitro</i> and <i>in vivo</i>, and anticancer evaluation.","authors":"Srimathi JaganMoorthy, Pranav Raaj Subbarayan Ravichandar, Harini Ganesan, Balasubramanian Deepika, Pazhani Durgadevi, Arulsamy Arokyapraveen, Agnishwar Girigoswami, Koyeli Girigoswami","doi":"10.5599/admet.3203","DOIUrl":"https://doi.org/10.5599/admet.3203","url":null,"abstract":"<p><strong>Background and purpose: </strong>Cancer is one of the leading causes of death worldwide, failing to identify a complete cure. Liver cancer is the sixth most frequent cancer worldwide, and its cure is still not assured. Nanoparticles, especially the metal oxide nanoparticles, have been explored as anticancer agents in recent times. In an attempt to make the best use of waste, plantain peel, a byproduct of agriculture, was used to synthesize copper oxide nanoparticles.</p><p><strong>Experimental approach: </strong>The plantain peel extract was evaluated for its chemical composition by GC-MS analysis, which revealed a predominant presence of tetratetracontane. The copper oxide nanoparticles were characterized by UV-visible spectrophotometry, dynamic light scattering, zeta potential, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDAX). Bio-inertness was assessed using an MTT assay of fibroblasts, a haemolysis assay, and zebrafish embryo analysis. The anticancer activity against HepG2 cells was estimated.</p><p><strong>Key results: </strong>The absorption peak was found at 402 nm, the hydrodynamic diameter was 323 nm, the zeta potential was +10.74 mV, and a band gap of 1.3 eV. The SEM images showed a size range of 54 to 85 nm with a chrysanthemum-petal-like morphology. EDAX showed the presence of Cu and O, and the XRD and FTIR peaks corroborated with that of CuO. The result showed that up to a dose of 50 μg mL^-1, the nanoparticles did not induce any toxicity. Finally, the anticancer activity, evaluated using the HepG2 cell line, showed a dose-dependent cytotoxic effect with an IC50 of 26.20 μg mL^-1.</p><p><strong>Conclusion: </strong>The outcome of this study suggested that the synthesized copper oxide nanoparticles can be used at controlled doses to kill cancer cells. Further studies are needed using other cancer cell lines and <i>in vivo</i> cancer models.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"14 ","pages":"3203"},"PeriodicalIF":4.3,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832264","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":"Modelling an alternative lipophilicity scale of bisphenols using biomimetic chromatography: Relevance to membrane-driven baseline toxicity.","authors":"Krzesimir Ciura, Julia Nicman, Szymon Zdybel, Giacomo Russo, Lucia Grumetto, Katarzyna Ewa Greber, Anita Sosnowska, Joanna Dołżonek, Karolina Jagiello","doi":"10.5599/admet.3169","DOIUrl":"https://doi.org/10.5599/admet.3169","url":null,"abstract":"<p><strong>Background and purpose: </strong>Bisphenol A and its structural analogues are ubiquitous environmental contaminants and potential endocrine disruptors, creating a need for mechanistically relevant descriptors that support early hazard assessment. This study asked whether lipophilicity indices derived from biomimetic chromatography better reflect baseline toxicity and membrane-relevant behaviour of bisphenols than commonly used in silico log <i>P</i> / log <i>D</i> descriptors.</p><p><strong>Experimental approach: </strong>A set of 18 bisphenol derivatives was analysed using phosphatidylcholine- and sphingomyelin-functionalised stationary phases and a conventional C18 column to obtain chromatographic hydrophobicity indices, which were then compared with predicted log <i>P</i> / log <i>D</i> values and related to mechanistically diverse toxicity endpoints (in vitro cytotoxicity in mammalian cells, ex vivo cardiotoxicity assessed as vasodilation, and aquatic toxicity towards Daphnids).</p><p><strong>Key results: </strong>Biomimetic chromatographic indices showed consistently stronger and more coherent relationships with biological activity than theoretical descriptors. They also uniquely captured structural effects, such as positional isomerism, which were largely indistinguishable using theoretical lipophilicity indices.</p><p><strong>Conclusion: </strong>These findings support biomimetic chromatography as an early-tier IATA tool, providing membrane-relevant experimental indices linking bisphenol lipophilicity with baseline toxicity.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"14 ","pages":"3169"},"PeriodicalIF":4.3,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832288","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":"Neuroprotective cellular and molecular mechanisms of physical exercise on neurodegenerative diseases.","authors":"Saswati Swagatika Sahoo, Pratap Kumar Sahu, Nishigandha Sa, Anindita Behera","doi":"10.5599/admet.3058","DOIUrl":"https://doi.org/10.5599/admet.3058","url":null,"abstract":"<p><strong>Background: </strong>Neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's disease are characterized by a progressive loss of neuronal function and loss of synaptic capacity. Physical exercise (PE) is one of the non-clinical techniques for the management of brain health and neurodegeneration.</p><p><strong>Mechanisms: </strong>PE enhances the body's metabolic functions through cellular and molecular changes. It trades off metabolic functions, energy expenditure, and signalling processes to ensure physiological homeostasis and defence against disease. Exercise produces cascades, at the molecular level, including neurotrophic signalling, similar to those generated by drugs. It increases the levels of the brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1), and vascular endothelial growth factor (VEGF). These elements favour the growth of new neurons, vascular enlargement, and synaptic plasticity. PE also induces microglial cells to attain a neuroprotective, anti-inflammatory phenotype, reduces detrimental cytokines, promotes cellular clearance through autophagy, restores neurotransmitter homogenisation, and induces hippocampal cell formation. Collectively, it acts as a powerful modulator of health and brain activity.</p><p><strong>Implications: </strong>The aggregate processes enhance neuronal vulnerability to harm, aid cognitive functioning, and ensure the stability of neural networks.</p><p><strong>Conclusion: </strong>PE is an exciting additive therapy for preventing and treating various neurodegenerative disorders by orchestrating a diverse array of cellular and molecular responses.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"14 ","pages":"3058"},"PeriodicalIF":4.3,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832313","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":"Bayesian inference for integrated pharmacokinetic modelling of mitragynine and 7-hydroxymitragynine.","authors":"Dion Notario, Untung Gunawan, Pretty Falena Atmanda Kambira, Erna Wulandari, Eko Adi Prasetyanto","doi":"10.5599/admet.3170","DOIUrl":"10.5599/admet.3170","url":null,"abstract":"<p><strong>Background and purpose: </strong>Mitragynine is an active compound in kratom that is metabolized to the pharmacologically active 7-hydroxymitragynine, requiring an integrated pharmacokinetic approach to maintain plasma concentrations of both within the optimal range. This study aims to develop an integrated pharmacokinetic model of mitragynine and 7-hydroxymitragynine using Bayesian inference.</p><p><strong>Experimental approach: </strong>A secondary dataset of mitragynine and 7-hydroxymitragynine in healthy human plasma was extracted and used to construct a two-compartment pharmacokinetic model upon oral administration. Initial parameter estimation was performed using a deterministic model fit to determine prior parameters. Bayesian inference was performed using Hamiltonian Monte Carlo across four independent chains, each with 2,000 iterations.</p><p><strong>Key results: </strong>The prior distribution estimation indicated that the Markov Chain Monte Carlo chain had converged and attained stationarity, yielding many independent effective samples. In general, no correlation between pharmacokinetic parameters was found due to modelling errors. The posterior predictive check plot confirmed a good fit between the model and the data. Pharmacokinetic simulations of repeated administration have been successfully developed and used to predict essential parameters in repeated administration, such as accumulation factors, maximum plasma concentration, time to maximum concentration, minimum plasma concentration, and area under the curve.</p><p><strong>Conclusion: </strong>The pharmacokinetics of mitragynine and 7-hydroxymitragynine were successfully modelled simultaneously with two compartments and proportional residuals using Bayesian inference with high accuracy.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"14 ","pages":"3170"},"PeriodicalIF":4.3,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12994590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147479569","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}