Xenobiotica最新文献_第2页

Defining the enzymes of xenobiotic metabolism - a forlorn hope? 定义异种代谢的酶-一个渺茫的希望？

IF 1.2 4区医学

Xenobiotica Pub Date : 2025-07-01 Epub Date: 2025-08-01 DOI: 10.1080/00498254.2025.2541003

Steve Mitchell, Rosemary Waring

引用次数: 0

Probe-substrate assay reveals the inhibition of CYP1A2, 2C9, and 3A4 by Senkyunolide A in human liver microsomes. 探针-底物测定显示仙球内酯A对人肝微粒体中CYP1A2、2C9和3A4的抑制作用。

IF 1.2 4区医学

Xenobiotica Pub Date : 2025-07-01 Epub Date: 2025-08-21 DOI: 10.1080/00498254.2025.2540396

Ruidong Wang, Tian Zuo, Yue Du, Jian Zai, Lijun Zhu, Qi Zhan

{"title":"Probe-substrate assay reveals the inhibition of CYP1A2, 2C9, and 3A4 by Senkyunolide A in human liver microsomes.","authors":"Ruidong Wang, Tian Zuo, Yue Du, Jian Zai, Lijun Zhu, Qi Zhan","doi":"10.1080/00498254.2025.2540396","DOIUrl":"10.1080/00498254.2025.2540396","url":null,"abstract":"Senkyunolide A (Sen A) has been shown to have neuroprotective effects, which leads to its inclusion in the daily diet of the elderly, thereby increasing the risk of adverse interactions with other drugs. To offer a reference for the clinical prescription and administration of Sen A, its impact on the activity of cytochrome P450 enzymes (CYP450s) was investigated.Pooled human liver microsomes were utilised to conduct the probe substrate assay. Concentration-dependent and time-dependent evaluation was carried out with 0 - 100 μM of Sen A and incubation time of 0-30 min. The inhibition of CYP450s was fitted with competitive or non-competitive inhibition models to characterise the effects of Sen A.Sen A significantly inhibited the activities of CYP1A2, 2C9, and 3A4 with IC50 values of 16.59, 14.73, and 11.51 μM, respectively. Both the inhibition of CYP1A2 and 2C9 followed a competitive pattern with the Ki values of 7.08 and 6.56 μM, respectively. In contrast, the inhibition of CYP3A4 was non-competitive (Ki = 5.19 μM) and time-dependent with the KI and Kinact of 0.404 μM-1 and 0.013 min-1, respectively.Careful administration of Sen A and related herbs is advised when used concurrently with drugs metabolised by CYP1A2, 2C9, and 3A4.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"566-571"},"PeriodicalIF":1.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849258","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}

引用次数: 0

Crack cocaine exposure leads to developmental alterations and mitochondrial dysfunction in the Drosophila melanogaster model. 在黑腹果蝇模型中，快克可卡因暴露导致发育改变和线粒体功能障碍。

IF 1.2 4区医学

Xenobiotica Pub Date : 2025-07-01 Epub Date: 2025-09-02 DOI: 10.1080/00498254.2025.2547613

Carlos Antônio Couto-Lima, Isa Rafaella Rocha Brito, Jucilene Freitas-Santos, Igor Santana-Melo, Kellysson Bruno Oliveira, Keylla Lavínia da Silva Oliveira, Bianca Rodrigues Melo da Silva, Amanda Larissa Dias Pacheco, Marcos Túlio Oliveira, Luciana Rosa de Souza Floresta, Carla Moura da Silva, Francisco Rubens Alves Dos Santos, Jerusa Maria de Oliveira, Jean Phellipe Marques do Nascimento, Mykaella Andrade de Araújo, Eurípedes Alves da Silva Filho, Olagide Wagner de Castro, Lucas Anhezini

{"title":"Crack cocaine exposure leads to developmental alterations and mitochondrial dysfunction in the Drosophila melanogaster model.","authors":"Carlos Antônio Couto-Lima, Isa Rafaella Rocha Brito, Jucilene Freitas-Santos, Igor Santana-Melo, Kellysson Bruno Oliveira, Keylla Lavínia da Silva Oliveira, Bianca Rodrigues Melo da Silva, Amanda Larissa Dias Pacheco, Marcos Túlio Oliveira, Luciana Rosa de Souza Floresta, Carla Moura da Silva, Francisco Rubens Alves Dos Santos, Jerusa Maria de Oliveira, Jean Phellipe Marques do Nascimento, Mykaella Andrade de Araújo, Eurípedes Alves da Silva Filho, Olagide Wagner de Castro, Lucas Anhezini","doi":"10.1080/00498254.2025.2547613","DOIUrl":"10.1080/00498254.2025.2547613","url":null,"abstract":"Crack cocaine is a highly addictive drug that may induce a plethora of health problems in users.The underlying pathophysiological and toxicity mechanisms promoted by crack cocaine use are still unclear.Here, we used the Drosophila melanogaster model to evaluate the dose-dependent effects of crack cocaine ingestion on several developmental and lifelong parameters, as well as the expression levels of key mitochondrial, endoplasmic reticulum, and antioxidant genes.Canton-S flies were fed increasing concentrations of crack cocaine and subjected to development, longevity, and negative geotaxis assays.Subsequently, we analyzed gene expression in L3 larvae and adult heads by quantitative real-time PCR. Crack cocaine increased larval lethality (>80%), and it affected the locomotor abilities of both larvae and adults (20-30%).This was associated with increased levels of mtDNA and transcripts for Marf, Pink1, Catalase, and Sod2 at low concentrations, suggesting mitochondrial biogenesis and remodelling.Mitochondrial and ER stress were evident at high crack concentrations, as indicated by a decrease in mtDNA copy number and increased transcript levels of parkin, spargel, Ire1, PEK, and CaMKII.Taken together, our data suggest that crack cocaine may lead to distinct harmful effects that are often apparent at very low doses, increasing adverse outcomes at high doses.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"543-553"},"PeriodicalIF":1.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144875461","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}

引用次数: 0

Neurotoxic mechanisms of the pesticide myclobutanil: integration of network toxicology, transcriptomics, and molecular simulation. 农药丁腈的神经毒性机制：网络毒理学、转录组学和分子模拟的整合。

IF 1.2 4区医学

Xenobiotica Pub Date : 2025-07-01 Epub Date: 2025-09-04 DOI: 10.1080/00498254.2025.2550363

Jiaxin Zhou, Jianping Hu, Na Tian, Yingying Zhang, Chunshuang Shang

{"title":"Neurotoxic mechanisms of the pesticide myclobutanil: integration of network toxicology, transcriptomics, and molecular simulation.","authors":"Jiaxin Zhou, Jianping Hu, Na Tian, Yingying Zhang, Chunshuang Shang","doi":"10.1080/00498254.2025.2550363","DOIUrl":"10.1080/00498254.2025.2550363","url":null,"abstract":"Myclobutanil, a pesticide commonly employed in agricultural practices for fruits, vegetables, and crops, is capable of crossing the blood-brain barrier (BBB) and persisting in cerebrospinal fluid, posing significant risks to human health. Consequently, it is crucial to systematically explore the molecular toxicological mechanisms underlying its neurotoxic effects.This study employed a systems-level approach that integrated weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network construction, followed by molecular docking and molecular dynamics (MD) simulations for validation.A total of 75 key targets were identified using cheminformatics tools (SEA, SwissTargetPrediction, TargetNet) and disease databases (GeneCards, OMIM, DisGeNET). Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis revealed that Myclobutanil exposure induces neurotoxicity through multiple signalling pathways, particularly the Pathways of neurodegeneration-multiple diseases and PI3K-Akt signalling pathway.Transcriptomic analysis and WGCNA identified RAF1 as a significantly correlated target with Myclobutanil exposure. Molecular docking and MD simulations further confirmed a strong binding affinity between RAF1 and Myclobutanil, suggesting that RAF1 plays a pivotal role in Myclobutanil exposure neurotoxicity.This prospective study yields predictive insight into the molecular events underlying Myclobutanil exposure neurotoxicity and highlights candidate therapeutic targets that remain to be validated in vivo.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"572-585"},"PeriodicalIF":1.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144971430","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}

引用次数: 0

Bidirectional relationship between statins and the gut microbiota: implications for cardiovascular health, diabetes, and cancer. 他汀类药物与肠道微生物群的双向关系：对心血管健康、糖尿病和癌症的影响。

IF 1.2 4区医学

Xenobiotica Pub Date : 2025-07-01 Epub Date: 2025-07-24 DOI: 10.1080/00498254.2025.2535445

Francisco Alejandro Lagunas-Rangel

{"title":"Bidirectional relationship between statins and the gut microbiota: implications for cardiovascular health, diabetes, and cancer.","authors":"Francisco Alejandro Lagunas-Rangel","doi":"10.1080/00498254.2025.2535445","DOIUrl":"10.1080/00498254.2025.2535445","url":null,"abstract":"Statins, which inhibit HMG-CoA reductase, are widely prescribed for cardiovascular disease prevention, while the gut microbiota plays a key role in host metabolism, immune regulation, and drug response.This narrative review examines how statins modulate the composition and function of the gut microbiota and, conversely, how the gut microbiota influences the pharmacokinetics, efficacy, and adverse effects of statins.Preclinical and clinical studies indicate that individual statins exert distinct effects; however, detailed understanding remains limited because these drugs are frequently evaluated collectively as a class rather than as separate compounds.Statins have been shown to alter microbial diversity and their metabolite profiles, which may enhance lipid-lowering effects and confer additional benefits such as anticancer activity, but may also contribute to adverse effects such as increased risk of type 2 diabetes. On the other hand, gut microbes modulate the bioavailability of statins by metabolizing the active compounds, which affects the therapeutic response.These results highlight the clinical importance of the gut microbiota in shaping the efficacy and safety profiles of statins and support the development of personalized, microbiome-informed treatment strategies.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"554-565"},"PeriodicalIF":1.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668637","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}

引用次数: 0

EP300/HIF-1 pathway: the key to sacubitril valsartan sodium alleviating myocardial hypoxia injury. EP300/HIF-1通路：苏比利缬沙坦钠减轻心肌缺氧损伤的关键

IF 1.2 4区医学

Xenobiotica Pub Date : 2025-06-01 Epub Date: 2025-07-22 DOI: 10.1080/00498254.2025.2528516

Jianyun Fang, Dan Yang, Fan Liu, Rong Xiao, Youqing Liang, Jiong Tang

{"title":"EP300/HIF-1 pathway: the key to sacubitril valsartan sodium alleviating myocardial hypoxia injury.","authors":"Jianyun Fang, Dan Yang, Fan Liu, Rong Xiao, Youqing Liang, Jiong Tang","doi":"10.1080/00498254.2025.2528516","DOIUrl":"10.1080/00498254.2025.2528516","url":null,"abstract":"Exploring the molecular mechanism underlying the pathogenesis and treatment of ischaemic cardiomyopathy (ICM) is crucial for its precise management.In this study, an ICM cell model was constructed, treated with sacubitril/valsartan, and subjected to exogenous modulation of EP300 expression. RT-qPCR and Western blot were employed to detect the expression of E1A-associated protein P300 (EP300), Hypoxia-Inducible Factor-1 (HIF-1) α, and HIF-1β. Additionally, the CCK-8 assay, flow cytometry, lactic acid detection, and ROS activity detection were used to examine changes in cell conditions. The aim was to verify the molecular mechanism of sacubitril/valsartan in treating ICM and explore the mechanism of targeting EP300 in ICM treatment.Results showed that sacubitril/valsartan upregulated EP300 expression, activated the EP300/HIF-1 signalling pathway, inhibited lactate secretion and ROS production, increased cell viability, and decreased the apoptosis rate in the ICM cell model. Direct upregulation of EP300 expression produced similar effects on the ICM cell model as sacubitril/valsartan.The mechanism by which sacubitril/valsartan reduces myocardial hypoxic injury by upregulating the EP300/HIF-1 signalling pathway suggests that targeting the EP300/HIF-1 signalling pathway may become a new approach for the treatment of ICM.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"478-487"},"PeriodicalIF":1.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592398","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}

引用次数: 0

Effects of ABCG2 421C > A genetic polymorphism on the pharmacokinetics of rivaroxaban in healthy Chinese subjects. ABCG2 421C > A基因多态性对中国健康人利伐沙班药代动力学的影响

IF 1.2 4区医学

Xenobiotica Pub Date : 2025-06-01 Epub Date: 2025-07-07 DOI: 10.1080/00498254.2025.2522731

Lingfang Guo, Xue Sun, Qiu Bo, Wanjun Bai, Yabin Du, Haojing Song

{"title":"Effects of ABCG2 421C > A genetic polymorphism on the pharmacokinetics of rivaroxaban in healthy Chinese subjects.","authors":"Lingfang Guo, Xue Sun, Qiu Bo, Wanjun Bai, Yabin Du, Haojing Song","doi":"10.1080/00498254.2025.2522731","DOIUrl":"10.1080/00498254.2025.2522731","url":null,"abstract":"The main objective of this study is to investigate whether the CYP3A4/5 and ABC transporter genetic polymorphisms could affect the pharmacokinetics (PK) of rivaroxaban in Chinese healthy subjects.Forty-two healthy subjects in China were recruited and given a single dose of 2.5 mg rivaroxaban tablets. Plasma concentration of rivaroxaban was determined by UPLC-MS/MS, the CYP3A4 20230 G > A(*1G)), CYP3A5 6986 A > G(*3), ABCB1 1236 C > T, ABCB1 3435 C > T, ABCB1 2677 G > T/A, ABCG2 34 G > A, ABCC2 1249 G > A, ABCC2 3972 C > T, ABCC2 - 24 C > T, ABCG2 421 C > A, SLC22A8 715 C > T, SLC22A8 445 C > A, SLC22A8 779 T > G, SLC22A8 829 C > T, and SLC22A8 913 A > T genotypes were determined by SnapShot Technique.In the study, compared with the subjects with C/C of ABCG2 421 C > A genotype, individuals with C/A and A/A genotype showed higher the area under the concentration-time curve AUC0-t (289.17 vs. 358.56 vs. 439.26 ng/h/mL) (p < 0.05 and p < 0.01, respectively), AUC0-∞ (293.92 vs. 362.80 vs. 442.25 ng/h/mL) (p < 0.05 and p < 0.01, respectively) and the maximum plasma concentration Cmax (56.58 vs. 70.36 vs. 83.90 ng/mL) (p < 0.05 and p < 0.01, respectively), but lower apparent clearance CL/F (9114.00 vs. 7493.82 vs. 6017.75 mL/h) (p < 0.05). Following Bonferroni correction, subjects carrying the A/A genotype continued to exhibit statistically significant differences in PK parameters Cmax, AUC0-t, and AUC0-∞ compared to C/C allele carriers.Data in the article proved that the ABCG2 421 C > A polymorphism was significantly related to the PK variability of rivaroxaban.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"445-453"},"PeriodicalIF":1.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144498185","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}

引用次数: 0

Hydrogen sulfide replenishment ameliorates impaired platelet response to clopidogrel in mice with experimental diabetes mellitus. 补充硫化氢可改善实验性糖尿病小鼠对氯吡格雷受损的血小板反应。

IF 1.2 4区医学

Xenobiotica Pub Date : 2025-06-01 Epub Date: 2025-07-31 DOI: 10.1080/00498254.2025.2534045

Ke Tang, Min Fu, Li-Ping Jiang, Ting Tai, Jin-Zi Ji, Xue-Mei Li, Yu Wu, Xiang-Hong Zhao, Pei-Jie Ding, Jin Wang, Zhao-Dong Zheng, Qiong-Yu Mi, Hong-Guang Xie

{"title":"Hydrogen sulfide replenishment ameliorates impaired platelet response to clopidogrel in mice with experimental diabetes mellitus.","authors":"Ke Tang, Min Fu, Li-Ping Jiang, Ting Tai, Jin-Zi Ji, Xue-Mei Li, Yu Wu, Xiang-Hong Zhao, Pei-Jie Ding, Jin Wang, Zhao-Dong Zheng, Qiong-Yu Mi, Hong-Guang Xie","doi":"10.1080/00498254.2025.2534045","DOIUrl":"10.1080/00498254.2025.2534045","url":null,"abstract":"This study aimed to reveal whether blood hydrogen sulfide (H2S) reduction could result in attenuated platelet inhibition of clopidogrel and whether replenishing blood H2S would reverse such attenuation in mice with diabetes mellitus (DM).Control (non-diabetic) versus DM mice were treated with vehicle control or GYY4137 (a synthetic H2S donor) alone or in combination with clopidogrel. Body weight gain, blood glucose, glucose tolerance, insulin tolerance, blood H2S, adenosine diphosphate (ADP)-induced whole-blood platelet aggregation, main clopidogrel metabolites (active thiol metabolite H4 and inactive clopidogrel carboxylate) in plasma, and the expression of main clopidogrel-metabolizing enzymes and interleukin-1β as well as their genes in the liver were measured, respectively.Compared with control mice, DM mice exhibited significant decreases in plasma H2S and H4 levels, glucose tolerance, insulin sensitivity, and clopidogrel-metabolizing enzyme expression, but significant increases in blood glucose, ADP-induced whole-blood platelet aggregation, and hepatic interleukin-1β expression, respectively. After use of GYY4137, boosting blood H2S levels ameliorated or reversed all other changes observed in DM mice, except for blood glucose elevation.Blood H2S reduction may contribute to impaired platelet inhibition of clopidogrel in DM mice, suggesting that replenishing blood H2S may benefit DM patients more when taking clopidogrel concomitantly.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"488-498"},"PeriodicalIF":1.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650643","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}

引用次数: 0

Sanguinarine-induced proteomic changes in methicillin-resistant Staphylococcus aureus. 血根碱诱导耐甲氧西林金黄色葡萄球菌的蛋白质组学改变。

IF 1.2 4区医学

Xenobiotica Pub Date : 2025-06-01 Epub Date: 2025-07-17 DOI: 10.1080/00498254.2025.2530998

Xiaolong Zhu, Pei Zhao, Lu Jiang, Yujuan Qi

{"title":"Sanguinarine-induced proteomic changes in methicillin-resistant Staphylococcus aureus.","authors":"Xiaolong Zhu, Pei Zhao, Lu Jiang, Yujuan Qi","doi":"10.1080/00498254.2025.2530998","DOIUrl":"10.1080/00498254.2025.2530998","url":null,"abstract":"The escalating threat of methicillin-resistant Staphylococcus aureus (MRSA) infections, coupled with the dwindling efficacy of current antibiotics, highlights the urgent need for novel antimicrobial agents.In this study, we demonstrate that sanguinarine - a plant-derived benzophenanthridine alkaloid - exerts potent antibacterial activity against MRSA, with a minimum inhibitory concentration (MIC) of 20 mg/L. To elucidate the molecular mechanisms underlying its antibacterial effects, we conducted a comprehensive, time-resolved proteomic analysis of MRSA upon sanguinarine exposure, quantifying a total of 1,037 proteins, among which significant alterations were observed at each time point over a 120-min treatment period. Proteomic profiling combined with fuzzy C-means clustering revealed distinct temporal response patterns. Upregulated proteins were enriched in pathways related to nucleotide excision repair and central metabolism, suggesting adaptive responses to DNA damage and metabolic stress. In contrast, downregulated proteins were primarily involved in critical cellular processes such as cell division, iron acquisition, RNA turnover, and protein synthesis, indicating a disruption of bacterial growth and homeostasis.These findings provide systems-level insights into the multifaceted antibacterial actions of sanguinarine and support its potential as a promising lead compound for the development of novel therapeutics targeting drug-resistant bacterial infections.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"454-463"},"PeriodicalIF":1.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144609744","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}

引用次数: 0

New era in bioequivalence global harmonization through ICH M13 initiative: critical review on new concepts, alternative approaches for high-risk products. 通过ICH M13倡议实现生物等效性全球统一的新时代：对高风险产品新概念和替代方法的批判性审查。

IF 1.2 4区医学

Xenobiotica Pub Date : 2025-06-01 Epub Date: 2025-07-30 DOI: 10.1080/00498254.2025.2535415

Mohammed Shareef Khan, Sohel Mohammed Khan, Frederico Severino Martins, Rajkumar Boddu, Anuj Kumar Saini, Sivacharan Kollipara

{"title":"New era in bioequivalence global harmonization through ICH M13 initiative: critical review on new concepts, alternative approaches for high-risk products.","authors":"Mohammed Shareef Khan, Sohel Mohammed Khan, Frederico Severino Martins, Rajkumar Boddu, Anuj Kumar Saini, Sivacharan Kollipara","doi":"10.1080/00498254.2025.2535415","DOIUrl":"10.1080/00498254.2025.2535415","url":null,"abstract":"Bioequivalence (BE) studies have made significant advancements, particularly with the introduction of the ICH M13 guidances. This review examines the historical aspects leading to the harmonisation efforts of the latest ICH M13A, the draft of ICH M13B, and the anticipated ICH M13C.The primary focus of this article is on ICH M13A, highlighting the significant changes over previous guidelines of USFDA and EMA. It outlines the stringent requirements for high-risk products as per ICH M13A and emphasises the necessity for both fasting and fed studies. This review highlights the high-risk complex formulations, such as amorphous solid dispersions, microemulsions, and nanotechnology-based formulations, which often exhibit different food effects compared to conventional formulations.Additionally, the role of PBPK/PBBM modelling in predicting food effects and fed bioequivalence for high-risk products is discussed. Furthermore, the potential of modelling based methodologies as 'alternative BE' approaches for securing waivers for fed BE studies is discussed in depth.Furthermore, the latest ICH M13B guidance is reviewed, focusing on differences from previous guidelines on dissolution similarity and bracketing approaches. The review also discusses the anticipated directions for ICH M13C and its potential impact on future BE studies for HVDs, NTIs, and complex designs.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"464-477"},"PeriodicalIF":1.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144660462","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}

引用次数: 0