Curr. Drug Metab. [JOURNAL]
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200 papers
Corrigendum to: Nanocochleates in Clinical Trials: A Review of Current Status, Challenges, and Future Directions.
Singh A, Verma S
Curr Drug Metab · 2026 · PMID 42374768 · Publisher ↗
In the article titled "Nanocochleates in Clinical Trials: A Review of Current Status, Challenges, and Future Directions", published in Current Drug Metabolism, 2025, 26(6), 390-401 [1], the in-text citation of references...
In the article titled "Nanocochleates in Clinical Trials: A Review of Current Status, Challenges, and Future Directions", published in Current Drug Metabolism, 2025, 26(6), 390-401 [1], the in-text citation of references [100, 101] was inadvertently included in Table 2 of the original version of the manuscript. The original article can be found online at: https://www.eurekaselect.com/article/150830.
Shenfu Decoction Extends Survival Time of Seawater-Induced Hypothermia in Rats: The Role of Metabolomics and Gut Microbiota.
Wang YJ, Chen HZ, Wang ZB … +7 more , Sun CY, Guo CY, Ruan Y, Li CT, Zou B, Yin ZF, Gu W
Curr Drug Metab · 2026 · PMID 42374767 · Full text
INTRODUCTION: Shenfu decoction (SFD), a Traditional Chinese Medicine formula, is used in clinical emergencies. Its effects on seawater-induced hypothermia remain unclear. This study investigates the therapeutic mechanism...
INTRODUCTION: Shenfu decoction (SFD), a Traditional Chinese Medicine formula, is used in clinical emergencies. Its effects on seawater-induced hypothermia remain unclear. This study investigates the therapeutic mechanisms of SFD in improving the survival of hypothermic rats through metabolomics and gut microbiota analysis. METHODS: Hypothermia was induced in rats via seawater immersion. The chemical constituents of SFD were analyzed using ultra-performance liquid chromatography quadrupole timeof- flight mass spectrometry (UPLC-Q-TOF-MS). Survival time and rates of low-temperature water-immersed rats were assessed. Rat blood samples were obtained for analysis of hematologic parameters, electrolytes, hepatic and renal function, cardiac injury, and inflammatory cytokines. To investigate the potential mechanism underlying the survival-prolonging effect of SFD on seawater-immersed hypothermic rats, untargeted blood metabolomics and gut microbiota profiling were employed for preliminary screening. RESULTS: UPLC-Q-TOF-MS identified almost 50 compounds in SFD, and 1.35 g/kg SFD significantly extended the survival time of seawater-induced hypothermia rats by 6 hours. After hypothermic seawater immersion, the levels of red blood cells, hemoglobin, hematocrit, as well as serum calcium, phosphorus, blood urea nitrogen, alkaline phosphatase, total protein, cardiac troponin T, and interleukin-6 were significantly increased. However, pretreatment with 1.35 g/kg SFD in rats markedly decreased these parameters. The induction of hypothermic seawater immersion elevated blood glucose, and the administration of SFD exacerbated this increase in rats. Metabolomic analysis revealed elevated levels of valerenic acid and benzoylmesaconine in the SFD group, suggesting the restoration of metabolic homeostasis. This recovery was associated with modulation of the gut microbiota, notably an enhancement of beneficial genera, such as Enterococcus. DISCUSSION: The findings demonstrated that SFD significantly prolonged survival in a rat model of seawater-immersion hypothermia. The protective mechanism involved a dual action: mitigating hypothermia-induced organ damage and hematological disturbances, coupled with restoring metabolic homeostasis and modulating gut microbiota. SFD has been found to possess specifically enriched beneficial bacterial genera, linked to the activation of brown adipose tissue and non-shivering thermogenesis. This study has provided initial evidence for a gut microbiota-metabolism axis mediating SFD's protective effect. CONCLUSION: SFD prolonged survival in rats with seawater-induced hypothermia, likely by enhancing thermogenesis and regulating lipid metabolism through gut microbiota changes. The findings highlighted the potential of SFD for hypothermia prevention; however, its exact underlying mechanisms require further validation.
Nucleic Acid Nanomaterials Targeting Autophagy in Bone Regeneration.
Yang X, Wang Y, Hu Z … +3 more , Geng J, Sun Y, Shao X
Curr Drug Metab · 2026 Jun · PMID 42312517 · Publisher ↗
Impairment or irreversible loss of bone tissue function remains a prevalent clinical challenge, frequently compounded by donor scarcity, perioperative infection, and immune-mediated rejection, which collectively constrai...
Impairment or irreversible loss of bone tissue function remains a prevalent clinical challenge, frequently compounded by donor scarcity, perioperative infection, and immune-mediated rejection, which collectively constrain therapeutic success rates. Novel functional nanomaterials based on nucleic acids-endowed with superior biocompatibility, predictable biodegradability, negligible systemic toxicity, and an abundance of programmable modification sites-have emerged as versatile platforms in bone tissue engineering. Currently, these materials are principally exploited across four interrelated domains: sustained release, bone targeting, scaffold materials for bone regeneration, and bioimaging, all aimed at orchestrating efficient bone regeneration. Recent mechanistic investigations into nano-bio interactions reveal that autophagy, a conserved catabolic pathway in eukaryotes that maintains energetic and metabolic homeostasis, critically governs skeletal repair by directing the timely degradation of intracellular cargo and the turnover of damaged organelles. Through direct modulation of osteoclast and osteoblast differentiation, autophagy fine-tunes the coupled process of bone remodeling. Concurrently, it shapes the regenerative milieu by reprogramming immune cell responses. Consequently, targeted modulation of autophagy represents a rational and promising strategy through which nucleic acid nanomaterials can accelerate bone regeneration. This review synthesizes current knowledge on the contributions of nucleic acid nanomaterials to bone healing, delineates the regulatory functions of autophagy in skeletal regeneration, and explains how these nanomaterials exploit autophagy as a mechanistic lever to enhance bone repair.
Nicotinamide N-Methyltransferase (NNMT): A Central Regulator in Hepatocellular Carcinoma Metabolism and Therapeutic Targeting - A Systematic Review.
Prajapati S, Yadav S, Singh AP
Curr Drug Metab · 2026 Jun · PMID 42260786 · Publisher ↗
INTRODUCTION: The purpose of this systematic review was to assess the expression of nicotinamide N-methyltransferase (NNMT), its mechanistic value, and clinical importance in Hepatocellular Carcinoma (HCC). METHODS: A se...
INTRODUCTION: The purpose of this systematic review was to assess the expression of nicotinamide N-methyltransferase (NNMT), its mechanistic value, and clinical importance in Hepatocellular Carcinoma (HCC). METHODS: A search was conducted in PubMed, Scopus, Web of Science, Google Scholar, and the Cochrane Library in accordance with PRISMA guidelines. Studies published between 2010 and 2024 that evaluated NNMT expression and its functional implications in HCC were included. Data extraction, synthesis, and qualitative analysis were performed according to standardized criteria. RESULTS: Sixty studies were included in this review. Most studies reported significantly higher NNMT overexpression in liver tumor tissue compared to non-tumor liver tissue. High NNMT levels were associated with aggressive tumor behavior, poor prognosis, and disruptions in methylation and energy metabolism. However, comparability across studies was limited due to heterogeneity in detection methods and small cohort sizes. DISCUSSION: The findings indicate that NNMT plays a crucial role in hepatocarcinogenesis by regulating methyl-donor balance and epigenetic remodeling. Although NNMT shows strong diagnostic and therapeutic potential, the current evidence is largely preclinical, high-lighting the need for multicenter validation. CONCLUSION: NNMT is a promising biomarker and therapeutic target for HCC. Future research should include quantitative assessment of NNMT expression, mechanistic validation, and clinical studies exploring NNMT inhibition strategies.
Chlorzoxazone-based One-Sample Method for Estimating In Vivo CYP2E1 Activity in Mice.
Zhang C, Yang R, Ma J … +6 more , Wang J, Jia L, Fang Y, Wen Q, Gao N, Qiao H
Curr Drug Metab · 2026 May · PMID 42099161 · Publisher ↗
INTRODUCTION: 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...
INTRODUCTION: 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. METHODS: 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. RESULTS: 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). DISCUSSION: 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. CONCLUSION: 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.
Unraveling the Gut Microbiota-Mediated Mechanism of Guogong Jiu for Rheumatoid Arthritis Treatment through Network Pharmacology and Metabolomics.
Yin Z, Li J, Zhao X … +6 more , Jia J, Lin Z, Zuo Z, Wang Z, Wang Z, Zhang J
Curr Drug Metab · 2026 May · PMID 42099160 · Publisher ↗
INTRODUCTION: 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 arthriti...
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. CONCLUSION: 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.
Cytochrome P450-derived Polyunsaturated Fatty Acid Metabolites as Modulators of Tumoral Hypoxia-induced Angiogenesis: From Mechanism to Anticancer Therapeutic Perspectives.
Torres-Zárate C, Santes-Palacios R
Curr Drug Metab · 2026 May · PMID 42099159 · Publisher ↗
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...
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.
Advancing MET-Aberrant NSCLC Therapy with Glumetinib: Pharmacokinetics, Efficacy, Safety, Drug Interactions, and Clinical Prospects.
Lu M, Yin X, Zhang Z
Curr Drug Metab · 2026 Apr · PMID 42059212 · Publisher ↗
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 mu...
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.
Mobilising Computational Strategies in Enzyme Inhibition: Reconciling Therapeutic Innovation and Environmental Integrity from Molecular Targets to Ecosystem Disruptors.
T M, Gowda J, M R … +2 more , Goudanavar P, Akondi BR
Curr Drug Metab · 2026 Apr · PMID 42051102 · Publisher ↗
Enzyme inhibition has become a cornerstone of modern therapeutics, targeting key molecular pathways implicated in cancer, metabolic disorders, and infectious diseases. This review explores diverse strategies of enzyme in...
Enzyme inhibition has become a cornerstone of modern therapeutics, targeting key molecular pathways implicated in cancer, metabolic disorders, and infectious diseases. This review explores diverse strategies of enzyme inhibition from classical active site-directed inhibitors to innovative biofilm-targeting enzymatic cocktails, emphasising their clinical utility. Beyond medicine, enzyme inhibitors are routinely employed to modulate nitrogen fixation, methanogenesis, and microbial dynamics in industrial and environmental settings. However, this dual-edged sword reveals its paradox: the very agent that heals can also harm. Their ecological persistence and bioaccumulation risks disrupt microbial ecosystems, foster antibiotic resistance, and affect non-target organisms. This review navigates the fine line between pharmaco-logical promise and environmental peril, evaluating risk assessment frameworks, mitigation strategies, and forward-looking approaches such as high-throughput screening, machine learning, and enzyme engineering. Ultimately, it advocates for a symbiotic integration of pharmaceutical innovation and environmental stewardship to create eco-friendly strategies that can enhance therapeutic efficacy without compromising ecological balance.
Formulation and Characterization of CCD-based Optimized Geraniol-loaded Antidiabetic Niosomes.
Yadav NK, Mazumder R, Rani A … +1 more , Mishra R
Curr Drug Metab · 2026 Apr · PMID 42051101 · Publisher ↗
INTRODUCTION: 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 n...
INTRODUCTION: 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. METHOD: 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. RESULT: 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. DISCUSSION: 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. CONCLUSION: 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.
Network Pharmacology and Metabolomics to Uncover the Multi-Target Anti-Non-Small Cell Lung Cancer Mechanism of Baicalin Mediated by Purine Metabolism.
Liao J, Wang R, Bie Y … +3 more , Bao J, Wu Q, Cai Y
Curr Drug Metab · 2026 Apr · PMID 42003060 · Publisher ↗
OBJECTIVE: 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...
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. CONCLUSION: 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.
Absorption, Distribution, Metabolism, and Excretion of [14C]MT-8, A Derivative of Procyanidin B3 in Sprague-Dawley Rats.
Xu H, Li Z, Wang L … +9 more , Zhang H, Chen S, Chen L, Gao Y, Zhao Y, Bao Y, Diao X, Chang J, Tang C
Curr Drug Metab · 2026 Apr · PMID 42003059 · Publisher ↗
INTRODUCTION/OBJECTIVES: Procyanidins are abundant dietary flavonoids with diverse pharmacological activities; however, their Absorption, Distribution, Metabolism, and Excretion (ADME) remain incompletely characterized....
INTRODUCTION/OBJECTIVES: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. CONCLUSION: Collectively, MT-8 undergoes rapid clearance, broad distribution, extensive metabolism, and predominant biliary/fecal excretion. These finding.
Constant-Speed Intravenous Infusion Model Determines Pharmacokinetic Parameters: Phylloquinone as an Example.
Mi YN, Yan PP, Fang ZJ … +6 more , Hui MQ, Cao L, Li QG, Xue FX, Liu JP, Cao YX
Curr Drug Metab · 2026 Apr · PMID 42003058 · Publisher ↗
INTRODUCTION: 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 th...
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. CONCLUSION: 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.
Strain Evaluation and Multi-Generational Stability of Cordyceps militaris for Functional Bioactive Compound Production.
Thi Gam D, Ngoc Minh T, Khac Hung N … +8 more , Thuy Diep N, Thi Thuy T, Thi Dung K, Thi Thanh Ha D, Thi Phuong Doai N, Tien Phat D, Thi Huyen T, Huu Trung K
Curr Drug Metab · 2026 Apr · PMID 42003057 · Publisher ↗
BACKGROUND: Cordyceps militaris is a medicinal fungus known for producing bioactive compounds, including cordycepin, adenosine, and polysaccharides, that exhibit antioxidant, immunomodulatory, and anticancer properties....
BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. CONCLUSION: KTDT8 represents a genetically stable, high-yielding strain with strong antioxidant properties, supporting its potential for large-scale pharmaceutical and nutraceutical applications.
Emerging Nanoformulation-Based Carrier Systems: New Insights into Promising Vaccine Delivery.
Rajpoot K
Curr Drug Metab · 2026 Apr · PMID 42003056 · Publisher ↗
INTRODUCTION: 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...
INTRODUCTION: 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. METHODS: 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. RESULTS: This review provides detailed updates on various nanoformulations, including chi-tosan NPs, alginate nanocarriers, liposomes, and emulsions, that are employed as vaccine delivery systems. DISCUSSION: 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. CONCLUSION: 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.
In Vitro Drug-Drug Interactions between Oxycodone and Commonly Co-Consumed Drugs in Rat and Human Liver Microsomes.
Gu W, Tyndale RF
Curr Drug Metab · 2026 Mar · PMID 41992412 · Publisher ↗
INTRODUCTION: Oxycodone is frequently co-consumed with xylazine, etizolam, di-azepam, and methamphetamine during clinical and/or illicit use. METHODS: We investigated oxycodone metabolism to its two main metabolites, the...
INTRODUCTION: Oxycodone is frequently co-consumed with xylazine, etizolam, di-azepam, and methamphetamine during clinical and/or illicit use. METHODS: We investigated oxycodone metabolism to its two main metabolites, the active ox-ymorphone and the inactive noroxycodone, and potential interactions with these four drugs, using rat (RLM) and human (HLM) liver microsomes. RESULTS: In RLM, Km values were similar for oxymorphone (115 μM) and noroxycodone (128 μM) formation, whereas in HLM, Km values differed for oxymorphone (146 μM) and noroxycodone (1.23 mM) formation. The CLint of oxycodone to noroxycodone was ~4-fold higher than oxycodone to oxymorphone, in both RLM and HLM. Xylazine inhibits (Ki) ox-ymorphone (1.9 μM) and noroxycodone (4.4 μM) formation in RLM more potently than in HLM (313 μM and 247 μM, respectively). Diazepam inhibits oxymorphone (5.0 μM) and no-roxycodone (5.6 μM) formation in RLM more potently than in HLM (1.8 mM and 163 μM, respectively). Etizolam inhibits oxymorphone (14.2 μM) and noroxycodone (16.1 μM) for-mation in RLM more potently than in HLM (550 μM and 129 μM, respectively). Metham-phetamine is not a potent inhibitor of oxymorphone formation (487 μM in RLM and 352 μM in HLM) or noroxycodone formation (5.8 mM in RLM and 2.7 mM in HLM). Similar inhi-bition patterns in RLM for both oxycodone and dextromethorphan, a probe substrate, con-firmed that CYP2D and CYP3A mediate oxymorphone and noroxycodone formation, respec-tively. DISCUSSION: In summary, xylazine, diazepam, and etizolam may cause pharmacokinetic drug-drug interactions (PK-DDIs) with oxycodone in rats but are unlikely to do so in humans. CONCLUSION: Substantial species differences were observed in both the metabolism of oxyco-done by CYP2D and CYP3A and the inhibition of metabolite formation in RLM versus HLM.
Protective Role of Atriplex halimus L. Against Sodium Benzoate-Induced Fat Benzene Accumulation, Bone Marrow and Liver Alterations in Wistar Rats.
Zeghib K, Boutlelis DA, Laib I … +4 more , Menai S, Bouafia A, Nani S, Rebiai A
Curr Drug Metab · 2026 Apr · PMID 41968859 · Publisher ↗
INTRODUCTION/OBJECTIVE: This study evaluates the adverse effects of sodium benzoate on the bone marrow and liver of rats, its potential to form benzene, and the protective role of Atriplex halimus extract. METHODS: Thirt...
INTRODUCTION/OBJECTIVE: This study evaluates the adverse effects of sodium benzoate on the bone marrow and liver of rats, its potential to form benzene, and the protective role of Atriplex halimus extract. METHODS: Thirty male albino rats were divided into five groups: control, Atriplex halimus extract alone, sodium benzoate alone, sodium benzoate with preventive Atriplex halimus ex-tract, and sodium benzoate with curative Atriplex halimus extract. Sodium benzoate was administered in drinking water at a dose of 100 mg/kg body weight for 15 weeks. Atriplex halimus extract was administered intragastrically either during the final 30 days (curative) or throughout the entire sodium benzoate exposure period (preventive). Phytochemical analysis of the extract was conducted using LC-MS. Biochemical, histopathological, and oxidative stress markers were assessed. RESULTS: Sodium benzoate exposure led to benzene detection in fat tissues, reduced neutrophil counts, altered hepatic enzyme levels (aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase), decreased antioxidant defenses (glutathione, catalase, glutathione S-transferase), and increased malondialdehyde levels. Histopathological analysis revealed significant liver degeneration and milder bone marrow damage. Atriplex halimus extract restored biochemical and histological parameters, reversed neutropenia, and reduced benzene accumulation. DISCUSSION: The findings confirm sodium benzoate's toxicity, particularly its oxidative stress and tissue damage effects, and highlight the protective potential of Atriplex halimus extract due to its phenolic compounds and saponins. CONCLUSION: Atriplex halimus extract exhibits preventive and curative effects against sodium benzoate-induced benzene accumulation in fat, as well as bone marrow and liver injuries.
Deciphering the Impact of Protein Corona on Biological Fate of Nanomedicine-Loaded Microneedles.
Zhu J, Wang W, Huang Z
Curr Drug Metab · 2026 Mar · PMID 41918203 · Publisher ↗
Due to adsorption of proteins, abundant protein molecules quickly bind to the nano-particles' (NPs) surface when they enter the bloodstream, forming a "protein corona." The protein corona leads to rapid clearance of NPs,...
Due to adsorption of proteins, abundant protein molecules quickly bind to the nano-particles' (NPs) surface when they enter the bloodstream, forming a "protein corona." The protein corona leads to rapid clearance of NPs, thereby impeding efficient drug delivery. Notably, mi-croneedles (MNs) can reduce protein corona formation by altering the route of drug entry and confining the drug within the local tissue microenvironment. This article outlines the relationship between drug-loaded MNs and the protein corona and proposes strategies to suppress its for-mation. Furthermore, it underscores that the synergy between microneedles and stealth nanocar-riers can minimize the detrimental effects associated with protein corona formation.
Development and Evaluation of a Baicalin-Loaded Phytosomal Transdermal Patch for Type 2 Diabetes Mellitus.
Singhal P, Mazumder R, Rani A … +1 more , Debnath A
Curr Drug Metab · 2026 Mar · PMID 41879453 · Publisher ↗
INTRODUCTION: Type 2 diabetes management remains challenging because of low bioavailability, side effects, and poor compliance with oral therapies. Transdermal delivery methods offer a non-invasive therapeutic approach w...
INTRODUCTION: Type 2 diabetes management remains challenging because of low bioavailability, side effects, and poor compliance with oral therapies. Transdermal delivery methods offer a non-invasive therapeutic approach with sustained delivery, which avoids first-pass metabolism. METHODS: A total of 207 different phytochemicals were virtually screened using i-dock against the diabetic target, PPAR-γ. Subsequently, three matrix-type transdermal patches were developed: a patch containing pure baicalin, a standard patch containing metformin, and a baicalin-loaded phytosomal patch. Phytosomes loaded with baicalin were optimized by using Central Composite Design and evaluated for their physicochemical properties, drug content, physical strength, in vitro, and ex vivo studies. In vivo antidiabetic efficacy was also studied in diabetic Wistar rats over 21 days, followed by a comparison of all formulations, including histopathological analysis of pancreatic tissue. RESULTS: Molecular docking studies showed promising results; baicalin has a high binding affinity for PPAR-γ (-9.8 kcal/mol). The optimized phytosomal patch confirmed a uniform drug content (91.4 ± 0.12 %) and showed sustained release over 12 hours. The ex vivo permeation study showed a significantly higher skin flux for the phytosomal patch (83.6%). In vivo studies confirmed that baicalin-loaded phytosomal patches showed significant blood glucose reductions (223 ± 0.32 to 96 ± 0.38 levels by Day 21), a comparable efficacy to standard metformin patches (224 ± 0.37mg/dL to 94 ± 0.34 mg/dL by Day 21). DISCUSSION: The enhanced skin permeation, penetration, and sustained-release exhibited by the phytosomal transdermal patch can be explained by the phospholipid-based shell structure, leading to better affinity with the skin, facilitating retention of the drug. The comparable glycemic control observed with metformin indicates that baicalin-loaded phytosomal transder-mal patches can achieve effective therapeutic concentrations via transdermal delivery, which is corroborated across two studies. These observations are consistent with previous literature documenting improved solubility and bioavailability of plant-derived actives utilizing phyto-some-based systems, which have applicability for chronic metabolic diseases such as T2DM. CONCLUSION: The developed phytosomal transdermal patch showed sustained release, better permeation, and potent antidiabetic activity; thus, it offers an alternative to conventional T2DM therapies.
Population Pharmacokinetic Models of Oxypurinol in Adults: A Systematic Review.
Zairol Azwan FAA, Mohd Tahir NA, Mohd Saffian S … +2 more , Makmor-Bakry M, Mohamed Said MS
Curr Drug Metab · 2026 Mar · PMID 41879452 · Publisher ↗
INTRODUCTION: Allopurinol and its active metabolite, oxypurinol, reduce uric acid concentrations through xanthine oxidase inhibition by suppressing the conversion of hypoxanthine and xanthine. Oxypurinol plays a prominen...
INTRODUCTION: Allopurinol and its active metabolite, oxypurinol, reduce uric acid concentrations through xanthine oxidase inhibition by suppressing the conversion of hypoxanthine and xanthine. Oxypurinol plays a prominent role in allopurinol's pharmacological activity due to its longer elimination half-life. Despite decades of clinical use, establishing an optimal dosing strategy to consistently achieve the target serum uric acid concentration lower than 0.36 mmol L-1 remains challenging. This review aimed to summarize the development of population pharmacokinetic modeling for oxypurinol and analyze factors influencing its pharmacokinetic variability. METHODS: PubMed, Web of Science, and Scopus were systematically searched from database inception until January 2025, adhering to the PRISMA guideline. Studies were eligible if they involved oxypurinol population pharmacokinetic analyses in adults receiving allopurinol and employed nonlinear mixed-effects modeling. RESULTS: Eight studies met the inclusion criteria, mostly involving adult gout patients. Pharmacokinetic analyses of oxypurinol employed a one-compartment model, incorporating firstorder absorption and elimination, reporting clearance value of 0.60-1.74 L h-1 and volume of distribution 38.1-59.3 L. Covariates associated with oxypurinol clearance included creatinine clearance, body weight, normal fat mass, fat-free mass, ethnicity, genetic polymorphisms, and concomitant diuretics; whereas, total body weight was found as significant predictors for volume of distribution. DISCUSSIONS: Reported values for oxypurinol clearance and volume of distribution varied across studies. The small sample sizes and underrepresentation of certain populations, particularly Asians, restrict the generalizability of these findings. CONCLUSION: Further research involving larger, more diverse cohorts is needed to refine therapeutic drug monitoring and identify potential covariates across different populations to optimize allopurinol therapy.
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