Current drug metabolism最新文献

{"title":"Unraveling the Gut Microbiota-Mediated Mechanism of Guogong Jiu for Rheumatoid Arthritis Treatment through Network Pharmacology and Metabolomics.","authors":"Zhicheng Yin, Jie Li, Xue Zhao, Jun Jia, Zhaozhou Lin, Zeping Zuo, Zijian Wang, Zhibin Wang, Jiayu Zhang","doi":"10.2174/0113892002468265260415075737","DOIUrl":"https://doi.org/10.2174/0113892002468265260415075737","url":null,"abstract":"<p><strong>Introduction: </strong>Rheumatoid Arthritis (RA) is a chronic autoimmune inflammatory disease. Guogong Jiu (GGJ) is a classical traditional Chinese medicine formula that is widely used in clinical treatment of rheumatoid arthritis. Nevertheless, the gut microbiota and metabolic mechanisms have not been fully studied. The objective of this study was to elucidate the gut microbiota-mediated mechanisms by which GGJ alleviates RA using network pharmacology, metabolomics, and experimental approaches.</p><p><strong>Methods: </strong>A rat model of collagen-induced arthritis was established to assess anti-arthritic effects systemically. The arthritis index, histopathology, inflammatory cytokines, and gut microbiota analysis (16S rRNA) were assessed for their effects. The serum and fecal metabolomics were done using UHPLC-Q-Exactive MS/MS. Moreover, network pharmacology and secondary metabolome analysis were used to identify the active herbal components, potential targets, and pathways, which were validated in Rheumatoid Arthritis Fibroblast-Like Synoviocytes (RA-FLS) as well.</p><p><strong>Results: </strong>GGJ improved the symptoms of Rheumatoid arthritis. GGJ affected pathways involved in amino acid, lipid, and energy metabolism. Moreover, the assessment of gut micro-biota revealed that GGJ helped restore microbial equilibrium by augmenting beneficial bacteria populations, including Lactobacillus and Alloprevotella, alongside diminishing Prevotella abundance. An integrated analysis identified NF-κB, MAPK, and NRF2 as key targets, which were subsequently validated at the cellular level.</p><p><strong>Discussion: </strong>The multi-omics integration reveals that GGJ exerts its therapeutic effects through coordinated regulation of the gut-joint axis, involving microbiota restoration, metabolic reprogramming, and signaling pathways. These findings provide a mechanistic basis for the clinical application of GGJ in RA.</p><p><strong>Conclusion: </strong>GGJ is effective in RA through multi-target effects involving modulation of inflammatory signaling pathways, mediation of metabolic reprogramming, and restoration of gut microbiota. The clinical application of GGJ for RA is therefore scientifically supported.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytochrome P450-derived Polyunsaturated Fatty Acid Metabolites as Modulators of Tumoral Hypoxia-induced Angiogenesis: From Mechanism to Anticancer Therapeutic Perspectives.","authors":"Carmen Torres-Zárate, Rebeca Santes-Palacios","doi":"10.2174/0113892002461017260421073832","DOIUrl":"https://doi.org/10.2174/0113892002461017260421073832","url":null,"abstract":"<p><p>Polyunsaturated Fatty Acids (PUFAs) are essential components of the human diet and physiology. Their biotransformation generates bioactive metabolites with regulatory functions in inflammation, vascular homeostasis, and tumor progression. Among these, arachidonic acid derivatives mediated by cytochrome P450 (CYP) enzymes, such as Epoxyeicosatrienoic acids (EETs) and Hydroxyeicosatetraenoic acids (HETEs), have emerged as key modulators of angiogenesis in the hypoxic tumor microenvironment. This review addresses the metabolic mechanisms that regulate the conversion of PUFAs by the CYP2C, CYP2J, and CYP4A/F families, emphasizing their role in activating signaling pathways such as VEGF/VEGFR and HIF-1, which impact cell proliferation, migration, and survival. Likewise, the therapeutic implications of modulating these PUFAs-metabolizing enzymes are analyzed, including the potential of EETs and 20-HETE analogs as pharmacological targets, with a view to developing new strategies for hypoxia-induced angiogenesis in cancer cells.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chlorzoxazone-based One-Sample Method for Estimating In Vivo CYP2E1 Activity in Mice.","authors":"Cunzhen Zhang, Rui Yang, Jun Ma, Jiyao Wang, Lin Jia, Yan Fang, Qiang Wen, Na Gao, Hailing Qiao","doi":"10.2174/0113892002414713251211102027","DOIUrl":"https://doi.org/10.2174/0113892002414713251211102027","url":null,"abstract":"<p><strong>Introduction: </strong>Cytochrome P450 2E1 (CYP2E1) plays a crucial role in metabolism and disease, making it highly significant to establish a simpler, sensitive method for evaluating its in vivo activity compared to traditional pharmacokinetic (PK) parameters.</p><p><strong>Methods: </strong>A high-performance liquid chromatography-ultraviolet (HPLC-UV) method was developed and validated for determining chlorzoxazone (CZX) and its metabolite 6-hydroxy CZX (6-OH CZX) in plasma. Four mouse models with distinct CYP2E1 activity were constructed: high activity induced by isoniazid, and low activity via Q11 (a CYP2E1 inhibitor), Cyp2e1 knockout, or carbon tetrachloride (CCl₄). PK experiments were conducted, with activity changes verified by in vitro CYP2E1 protein expression and microsomal activity. Additionally, the sensitivity of PK parameters and the plasma 6-OH CZX/CZX ratio (metabolite ratio, MR) for characterizing CYP2E1 activity, as well as correlations between MR at different time points and both microsomal CYP2E1 activity and CZX half-life (t₁/₂), were analyzed.</p><p><strong>Results: </strong>The HPLC-UV method met analytical requirements in terms of specificity, linearity, and intra-day and inter-day precision. Microsomal activity and protein expression experiments confirmed the successful establishment of the four models. For CYP2E1 activity characterization, CZX t₁/₂ was more sensitive than its area under the curve (AUC) and clearance (CL); MR values at 15 and 7 minutes outperformed those at 2 minutes, with 15-minute MR showing stronger correlations with microsomal activity (r = 0.57, P = 0.007) and CZX t₁/₂ (r = 0.83, P < 0.01).</p><p><strong>Discussion: </strong>This study addresses limitations of traditional PK parameters (multiple samplings, non-metabolic interference) and existing MR methods (unclear optimal time points). The 15-min MR and CZX t₁/₂ offer simplified evaluation, with CZX's high CYP2E1 specificity enhancing translation. Limitations include focus on male C57BL/6J mice and single-point MR's inability to reflect dynamic activity.</p><p><strong>Conclusion: </strong>Four representative mouse models with distinct CYP2E1 activity were successfully constructed. CZX t₁/₂ exhibits higher sensitivity and applicability in characterizing in vivo CYP2E1 activity changes, while the 15-minute MR better represents activity changes. This research lays a foundation for characterizing CYP2E1 variations in disease and pathological processes.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing MET-Aberrant NSCLC Therapy with Glumetinib: Pharmacokinetics, Efficacy, Safety, Drug Interactions, and Clinical Prospects.","authors":"Ming Lu, Xiaoyu Yin, Zhiqing Zhang","doi":"10.2174/0113892002428815251201090233","DOIUrl":"https://doi.org/10.2174/0113892002428815251201090233","url":null,"abstract":"<p><p>Targeting Mesenchymal-Epithelial Transition Factor (MET) gene aberrations has emerged as a pivotal strategy in the precision treatment of Non-Small Cell Lung Cancer (NSCLC). Among these, MET exon 14 (METex14) skipping mutation represents a well-established and significant therapeutic target. Glumetinib, a highly selective oral MET inhibitor developed in China, has been approved by the National Medical Products Administration (NMPA) and the Pharmaceuticals and Medical Devices Agency (PMDA) for the treatment of advanced or relapsed NSCLC with METex 14 skipping mutation. Glumetinib has not yet received approval from the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA). However, a phase II clinical trial is ongoing in the United States, planning to enroll 78 patients with advanced c-MET-positive NSCLC, which may support future regulatory submissions. Preclinical investigations have shown that glumetinib effectively inhibits MET-driven tumors by specifically targeting c-Met kinase activity and its associated downstream signaling pathways. In the pivotal phase II GLORY trial, patients with METex14-positive NSCLC were administered glumetinib (300 mg/day) and demonstrated an Objective Response Rate (ORR) of 66% and a median Progression-Free Survival (PFS) of 8.5 months. Notably, patients with brain metastases exhibited an ORR of 85%. Treatment-Related Adverse Events (TRAEs) of grade≥3 severity were reported in 54% of patients, with only 8% discontinuing treatment due to TRAEs, suggesting a manageable safety profile. From the perspective of China's healthcare system, glumetinib is considered more cost-effective than savolitinib in treating NSCLC patients with METex14 skipping. The clinical applications of glumetinib are broadening to encompass strategies to overcome drug resistance and combination therapies. This manuscript seeks to provide a comprehensive overview of the essential characteristics, mechanism of action, pharmacokinetics, efficacy, safety, drug interactions, and cost-effectiveness of glumetinib while also exploring its future therapeutic potential.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network Pharmacology and Metabolomics to Uncover the Multi-Target Anti-Non-Small Cell Lung Cancer Mechanism of Baicalin Mediated by Purine Metabolism.","authors":"Jing Liao, Rui Wang, Yanan Bie, Junjun Bao, Qibiao Wu, Yu Cai","doi":"10.2174/0113892002446093260416220857","DOIUrl":"https://doi.org/10.2174/0113892002446093260416220857","url":null,"abstract":"<p><strong>Objective: </strong>Baicalin (BA), the primary active component of Scutellaria baicalensis, exhibits anti-tumor potential; however, its multi-target mechanism in the treatment of non-small cell lung cancer (NSCLC) remains poorly understood.</p><p><strong>Methods: </strong>This study systematically elucidated the anti-NSCLC mechanism of BA through an integrated approach that combined network pharmacology, molecular docking, molecular dynamics simulations, in vivo animal models, and untargeted metabolomics using LC-MS. Potential targets were predicted using SwissTargetPrediction and multiple disease databases. A protein-protein interaction (PPI) network was constructed and analyzed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Core targets were validated via molecular docking and simulations. The effects of BA on tumor growth and on the expression of EGFR and TNF-α were assessed in an A549 tumor-bearing nude mouse model. Serum metabolite changes were profiled and linked to associated pathways.</p><p><strong>Results: </strong>Sixty overlapping targets were identified, with EGFR, TNF-α, CASP3, PTGS2, EZH2, and IL-2 serving as core nodes. Molecular docking demonstrated strong binding affinity between BA and both EGFR (-9.830 kcal/mol) and PTGS2 (-7.244 kcal/mol). The in vivo xenograft model demonstrated that BA (2.5 mg/kg) significantly inhibited NSCLC tumor growth, with efficacy comparable to paclitaxel. Immunohistochemistry confirmed BA downregulated EGFR and TNF-α expression in tumors. Metabolomics analysis revealed 17 differentially expressed metabolites and four significantly altered metabolic pathways: purine, caffeine, sphingolipid, and pyrimidine metabolism. Purine metabolism exhibited the most pronounced perturbation.</p><p><strong>Discussion: </strong>The integrated analysis reveals that BA exerts its anti-NSCLC effects through a multi-target mechanism involving direct interactions with key signaling proteins, such as EGFR and PTGS2, downregulation of oncogenic and inflammatory pathways, and systemic reprogramming of cancer-associated metabolism, with purine metabolism as a central target.</p><p><strong>Conclusion: </strong>BA exerts its anti-NSCLC effects via multi-target regulation of oncogenic signaling and metabolic reprogramming. This offers preliminary insights that could inform future applications in metabolic-targeted therapies and combination treatments.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Nanoformulation-Based Carrier Systems: New Insights into Promising Vaccine Delivery.","authors":"Kuldeep Rajpoot","doi":"10.2174/0113892002396742251205101733","DOIUrl":"https://doi.org/10.2174/0113892002396742251205101733","url":null,"abstract":"<p><strong>Introduction: </strong>Vaccines are crucial for controlling infectious diseases and reducing reliance on antibiotics, yet many diseases still lack effective vaccines. Advances in nanomaterials engineering offer new opportunities for vaccine design, utilizing nanoparticles (NPs) to elicit immune responses and modulate adaptive immunity.</p><p><strong>Methods: </strong>A comprehensive search of online databases was conducted to gather research on emerging nanocarriers for vaccine delivery. The review focused on gold NPs, dendrimer-based vaccines, exosome-based vaccines, chitosan (CS) NPs in nasal vaccines, lipid NPs (LNPs) for vaccines against SARS-CoV-2, influenza, rabies, and cancer, solid lipid nanoparticles (SLNs) as vaccine adjuvants, emulsions, and liposome-based vaccines. The limitations of CS in industrial-scale nasal vaccine production were also considered.</p><p><strong>Results: </strong>This review provides detailed updates on various nanoformulations, including chi-tosan NPs, alginate nanocarriers, liposomes, and emulsions, that are employed as vaccine delivery systems.</p><p><strong>Discussion: </strong>Although nanomedicines are still in their infancy, they offer significant advantages, such as targeted delivery, controlled release, and enhanced immunogenicity. The development of nano-vaccines depends on a deeper understanding of their interactions with both the innate and adaptive immune systems.</p><p><strong>Conclusion: </strong>Nanotechnology has transformed the development of nanomedicines, enabling precise drug delivery and targeted therapy. Despite being at an early stage, these nanomedicines are reshaping the future of medicine by improving efficacy, reducing toxicity, and enhancing delivery to specific cells and tissues.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strain Evaluation and Multi-Generational Stability of Cordyceps militaris for Functional Bioactive Compound Production.","authors":"Do Thi Gam, Truong Ngoc Minh, Nguyen Khac Hung, Nguyen Thuy Diep, Tran Thi Thuy, Kieu Thi Dung, Dang Thi Thanh Ha, Nguyen Thi Phuong Doai, Do Tien Phat, Tran Thi Huyen, Khuat Huu Trung","doi":"10.2174/0113892002410536251027102107","DOIUrl":"https://doi.org/10.2174/0113892002410536251027102107","url":null,"abstract":"<p><strong>Background: </strong>Cordyceps militaris is a medicinal fungus known for producing bioactive compounds, including cordycepin, adenosine, and polysaccharides, that exhibit antioxidant, immunomodulatory, and anticancer properties. Enhancing production and ensuring the genetic stability of these metabolites are essential for therapeutic development.</p><p><strong>Objective: </strong>To evaluate growth characteristics, metabolite yield, antioxidant activity, and genetic stability of 20 C. militaris strains, and to identify high-performing, stable candidates suitable for pharmaceutical applications.</p><p><strong>Methods: </strong>Twenty C. militaris strains were cultured and analyzed for colony diameter, fruiting body morphology, biomass yield, and bioactive compound content. Antioxidant activity was assessed using the DPPH assay. Genetic stability was monitored over five generations via MAT gene profiling.</p><p><strong>Results: </strong>Strain KTDT8 showed superior performance with the highest levels of cordycepin (469.8 ± 16.4 mg/100 g), adenosine (121.8 ± 7.4 mg/100 g), and polysaccharides (37.0 ± 2.9 mg/g), and the strongest antioxidant activity (IC₅₀ = 31.2 μg/mL). The strain maintained morphological and genetic stability across four generations, with a moderate decline in the fifth.</p><p><strong>Discussion: </strong>KTDT8 consistently demonstrated superior metabolite yield, antioxidant capacity, and morphological stability across generations. Despite a moderate decline in biomass and fruiting body quality in the fifth generation, the strain retained its core phenotypic and genetic traits. These findings support KTDT8 as a viable candidate for long-term cultivation and bioactive compound production.</p><p><strong>Conclusion: </strong>KTDT8 represents a genetically stable, high-yielding strain with strong antioxidant properties, supporting its potential for large-scale pharmaceutical and nutraceutical applications.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Absorption, Distribution, Metabolism, and Excretion of [14C]MT-8, A Derivative of Procyanidin B3 in Sprague-Dawley Rats.","authors":"Haibo Xu, Zhiqiang Li, Linwei Wang, Heyanhao Zhang, Shuoyue Chen, Lijuan Chen, Yang Gao, Yuqing Zhao, Yuanwu Bao, Xingxing Diao, Jun Chang, Chongzhuang Tang","doi":"10.2174/0113892002454324260401050804","DOIUrl":"https://doi.org/10.2174/0113892002454324260401050804","url":null,"abstract":"<p><strong>Introduction/objectives: </strong>Procyanidins are abundant dietary flavonoids with diverse pharmacological activities; however, their Absorption, Distribution, Metabolism, and Excretion (ADME) remain incompletely characterized. MT-8, a procyanidin B3 derivative with an ethyl group at the C8 position of the A-ring, is a promising preclinical candidate for cerebral ischemia treatment and is currently in the Investigational New Drug (IND) application stage. This study aimed to systematically characterize the ADME profile of MT-8 in male Sprague-Dawley (SD) rats following intravenous administration to provide a reference for ADME studies of procyanidin-related compounds.</p><p><strong>Methods: </strong>A single intravenous dose of 24 mg/kg (100 μCi/kg) [¹⁴C]MT-8 was administered to male SD rats. Given the observed instability of MT-8 in plasma due to catechol oxidation, 10 mM tris(2-carboxyethyl) phosphine hydrochloride (TCEP) was employed as a stabilizer in all sample preparations. Pharmacokinetics, tissue distribution, mass balance, metabolite profiling, and metabolic enzyme phenotyping were comprehensively evaluated.</p><p><strong>Results: </strong>Pharmacokinetic analysis revealed rapid elimination of [¹⁴C]MT-8-related substances, with a terminal half-life of 1.77 hours. The blood-to-plasma radioactivity ratio (1.68) indicated preferential distribution into blood cells. Tissue distribution revealed the highest radioactivity concentrations in the small intestine, kidneys, and liver. Mass balance analysis showed total radioactive recovery of 95.49% within 168 hours, with clearance of >90% of drug-related substances within 24 hours, predominantly via feces (85.57%) and bile (62.78% in bile duct-cannulated rats), with only 9.91% in urine. Metabolite profiling identified 32 metabolites in plasma, urine, feces, and bile, with methylation and glucuronidation as the major metabolic pathways. In vitro phenotyping referred to catechol-O-methyltransferase (COMT) involvement in methylation and UDP-glucuronosyltransferase 1A1 (UGT1A1) and 1A9 (UGT1A9) in glucuronidation.</p><p><strong>Discussion: </strong>After verifying the mechanism of the instability of MT-8 in plasma, we tracked the in vivo disposition of MT-8 via radioisotope labeling technique and acquired credible pharmacokinetic, mass balance, tissue distribution, and metabolite identification results. Phenotypes of two enzymes were determined to further the investigation of the methylation and glucuronidation process of in vivo clearance of MT-8.</p><p><strong>Conclusion: </strong>Collectively, MT-8 undergoes rapid clearance, broad distribution, extensive metabolism, and predominant biliary/fecal excretion. These finding.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Constant-Speed Intravenous Infusion Model Determines Pharmacokinetic Parameters: Phylloquinone as an Example.","authors":"Yan-Ni Mi, Ping-Ping Yan, Zhi-Jian Fang, Ming-Quan Hui, Lei Cao, Qiong-Ge Li, Fei-Xiao Xue, Ji-Ping Liu, Yong-Xiao Cao","doi":"10.2174/0113892002447026260402063559","DOIUrl":"https://doi.org/10.2174/0113892002447026260402063559","url":null,"abstract":"<p><strong>Introduction: </strong>Reported pharmacokinetic parameters, particularly half-life (t1/2), show substantial variability for phylloquinone, due to the limitations of classical pharmacokinetic models. The study aims to determine the pharmacokinetic parameters of phylloquinone using a Constant-Speed Intravenous Infusion (CSII) strategy, designed to overcome the limitations of the low terminal-phase concentration quality following Intravenous (IV) bolus administration.</p><p><strong>Methods: </strong>The Sprague-Dawley rats received a constant-rate infusion of phylloquinone for 15 hours. Plasma concentrations were quantified by a validated HPLC method, and pharmacokinetic parameters following CSII were derived by fitting the data to a one-phase exponential association model.</p><p><strong>Results: </strong>Following CSII, phylloquinone exhibited a t1/2 of 4.27 ± 0.47 h, CL of 56.93 ± 9.00 mL/h, and Vd of 321.86 ± 29.25 mL without the limitation of low terminal-phase concentrations. Following IV, the t1/2 and Vd of phylloquinone based on two-compartment analysis were larger than those based on one-compartment analysis. Noncompartmental analysis revealed significant differences in t1/2 and Mean Residence Time (MRT) across varying sampling durations. Meanwhile, the t1/2 of phylloquinone was markedly different from its MRTequated half-life. Additionally, the Vd estimated after CSII was larger than that obtained from the IV bolus.</p><p><strong>Discussion: </strong>The CSII strategy avoids reliance on error-prone terminal-phase data by deriving the pharmacokinetic parameters from the ascending phase of the concentration-time profile. This approach provided robust parameter estimates and helped clarify inconsistencies observed with traditional IV bolus analyses.</p><p><strong>Conclusion: </strong>CSII provides a valuable complementary strategy for pharmacokinetic parameter estimation, especially for compounds with problematic terminal-phase analysis or those routinely given by CSII. Its broader applicability warrants further investigation.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formulation and Characterization of CCD-based Optimized Geraniol-loaded Antidiabetic Niosomes.","authors":"Nitesh Kumar Yadav, Rupa Mazumder, Anjna Rani, Rakhi Mishra","doi":"10.2174/0113892002382359251122043509","DOIUrl":"https://doi.org/10.2174/0113892002382359251122043509","url":null,"abstract":"<p><strong>Introduction: </strong>Type 2 Diabetes (T2D) presents a significant global health challenge, characterized by persistent hyperglycemia and insulin resistance, with effective long-term glycemic control remaining a critical unmet need. Geraniol, a naturally occurring monoterpene alcohol, holds promising anti-diabetic potential but is limited by poor water solubility, which restricts its therapeutic application. This study focuses on the formulation and CCD-based optimization of geraniol-loaded niosomes. Additionally, to assess its antidiabetic effect, blood glucose levels were evaluated.</p><p><strong>Method: </strong>Geraniol-loaded niosomes were formulated using the thin-film hydration technique. A central composite design was generated using Design Expert software to evaluate the impact of Span 40 and cholesterol concentrations on dependent variables such as particle size and encapsulation efficiency. A streptozotocin-induced diabetic model was used to assess the in vivo antidiabetic effect of the geraniol-loaded niosomes.</p><p><strong>Result: </strong>Using the thin-film hydration technique and CCD optimization, the niosomes demonstrated favorable characteristics, including an average particle size of 287.7 nm, an entrapment efficiency of 80.13%, and a zeta potential of -25.46 mV. Geraniol-loaded niosomes produced a notable hypoglycemic effect, reducing blood glucose levels from 275 ± 0.28 mg/dL to 150 ± 0.20 mg/dL by day 21. Although slightly less potent than metformin (117 ± 0.93 mg/dL), the formulation showed significantly better efficacy than both the diabetic control and plain geraniol solution groups.</p><p><strong>Discussion: </strong>Pharmacokinetic analysis revealed that the AUC, AUMC, and MRT of the geraniol-loaded niosomal formulation were approximately 1.5-, 4-, and 3-fold higher, respectively, compared to plain geraniol. These findings indicate that niosomal formulations improve bioavailability while providing sustained and prolonged drug release.</p><p><strong>Conclusion: </strong>Overall, these results highlight the potential of geraniol-loaded niosomes as an innovative and effective strategy for managing T2D, supporting further clinical research to explore their therapeutic application in addressing this global health challenge.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}