IF 1.3 4区医学

Xenobiotica Pub Date : 2025-05-29 DOI: 10.1080/00498254.2025.2508814

Hagar A Elmekawy, Khaled Abdelkawy, Galal Magdy, Emad Sadaka, Gamal El-Azab, Ahmed Ali, Noha El-Khodary, Fawzy Elbarbry

{"title":"Genetic polymorphisms of ABCC2 and CBR3 can influence the efficacy and toxicity of doxorubicin therapy in Egyptian patients with non-Hodgkin lymphoma.","authors":"Hagar A Elmekawy, Khaled Abdelkawy, Galal Magdy, Emad Sadaka, Gamal El-Azab, Ahmed Ali, Noha El-Khodary, Fawzy Elbarbry","doi":"10.1080/00498254.2025.2508814","DOIUrl":"10.1080/00498254.2025.2508814","url":null,"abstract":"This study investigated the impact of single nucleotide polymorphisms (SNPs) in genes involved in doxorubicin (DOX) transport and metabolism on clinical outcomes and toxicity in Egyptian patients with non-Hodgkin lymphoma.Ninety-two patients received at least six DOX treatment cycles. SNP genotyping was performed using real-time PCR with high-resolution melting analysis. Laboratory tests were conducted at baseline, during, and after treatment.The AA genotype of ABCC2 (rs8187710) showed the strongest association with elevated DOX plasma levels and a significantly increased risk of acute cardiotoxicity (OR 26.9; 95% CI: 1.47-492; p = 0.026). The GA genotype was linked to a lower complete response rate and increased risks of leukopoenia (OR 2.66; 95% CI: 1.07-6.61; p = 0.034) and lymphocytopenia (OR 10; 95% CI: 3.57-27.9; p < 0.0001), with intermediate peak DOX levels. For CBR3 (rs8133052), the GA genotype was significantly associated with a higher risk of anaemia (OR 3.5; 95% CI: 1.05-11.7; p = 0.042), acute cardiotoxicity (OR 4.4; 95% CI: 1.86-11.5; p = 0.002), cardiac-related symptoms, and higher peak plasma DOX levels, along with reduced complete response.Polymorphisms in ABCC2 and CBR3 genes may contribute to individual variability in DOX-related toxicity and treatment response.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-11"},"PeriodicalIF":1.3,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120981","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

Machine learning-driven bioavailability prediction in early-stage drug development: a KNIME-based computational workflow for digital health applications. 早期药物开发中机器学习驱动的生物利用度预测：用于数字健康应用的基于knime的计算工作流。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-05-28 DOI: 10.1080/00498254.2025.2508804

Majdi Hammami, Walid Yeddes, Hamza Gadhoumi, Raghda Yazidi, Moufida Saidani Tounsi, Kamel Msaada

{"title":"Machine learning-driven bioavailability prediction in early-stage drug development: a KNIME-based computational workflow for digital health applications.","authors":"Majdi Hammami, Walid Yeddes, Hamza Gadhoumi, Raghda Yazidi, Moufida Saidani Tounsi, Kamel Msaada","doi":"10.1080/00498254.2025.2508804","DOIUrl":"10.1080/00498254.2025.2508804","url":null,"abstract":"Bioavailability prediction remains a significant challenge in early-stage drug development, where conventional experimental approaches are time-consuming and resource-intensive. This study explores the application of machine learning techniques to enhance the efficiency of bioavailability prediction. By leveraging computational workflows within the KNIME Analytics Platform, we aim to automate bioavailability assessment and reduce dependence on costly in vitro and in vivo studies.A dataset comprising 475 drug-like compounds characterised by key molecular descriptors was analysed using multiple machine learning models, including Random Forest, Gradient Boosting, Decision Trees, k-Nearest Neighbours, and neural networks. Model performance was assessed through 5-fold cross-validation, with ensemble models outperforming linear and neural network-based approaches. Random Forest demonstrated the highest predictive performance (R2 = 0.87, RMSE = 0.08). Feature importance analysis identified topological polar surface area and solubility as the most influential factors in bioavailability prediction.The findings underscore the potential of integrating open-source tools and machine learning methodologies in pharmaceutical research, improving workflow efficiency while adhering to FAIR (Findable, Accessible, Interoperable, and Reusable) data principles. This approach facilitates rapid and cost-effective bioavailability assessment, supporting AI-driven predictive modelling and digital health applications in drug development.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-10"},"PeriodicalIF":1.3,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112216","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

Meeting report: DMDG peptide and oligonucleotide ADME workshop 2024. 会议报告：DMDG肽和寡核苷酸ADME研讨会2024。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-05-28 DOI: 10.1080/00498254.2025.2506702

Inga Bjørnsdottir, Ralf Lotz, Bo Lindmark, Steve Hood, Jesper Kammersgaard Christensen

引用次数: 0

Exploring ethanol's toxicity in the oral submucosa: chronic exposure versus abstinence in C57BL/6 mice. 探索乙醇在口腔黏膜下的毒性：C57BL/6小鼠的慢性暴露与戒断。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-05-25 DOI: 10.1080/00498254.2025.2505066

Devaraj Ezhilarasan, Karthik Shree Harini, Karthick Munusamy

{"title":"Exploring ethanol's toxicity in the oral submucosa: chronic exposure versus abstinence in C57BL/6 mice.","authors":"Devaraj Ezhilarasan, Karthik Shree Harini, Karthick Munusamy","doi":"10.1080/00498254.2025.2505066","DOIUrl":"10.1080/00498254.2025.2505066","url":null,"abstract":"Alcohol consumption is a recognised risk factor for the development of precancerous lesions in the oral cavity. This study investigates the effects of chronic ethanol exposure on inflammation and fibrosis in mice.Eighteen C57BL/6 mice were divided into three groups: Group I received only drinking water, while Groups II and III were exposed to 25% ethanol ad libitum for 14 weeks. Group II mice were sacrificed at the end of the 14th week, whereas Group III underwent a 4-week abstinence period before sacrifice. Gene expression related to inflammation and fibrosis, along with histopathological changes in submucosal tissue, was analysed.Chronic ethanol exposure significantly upregulated MAPK signalling markers, as well as inflammatory and fibrotic markers, in submucosal tissue. In Group III, inflammatory markers such as NF-κB, p65, NLRP3, and caspase-1 partially returned to normal levels after abstinence, whereas fibrotic markers, particularly MMP-9, remained elevated. Histopathological analysis of oral submucosa revealed epithelial atrophy and extracellular matrix accumulation in ethanol-exposed mice.These findings suggest that 14 weeks of ethanol exposure induces persistent epithelial damage, inflammation, and fibrosis in the oral submucosa, with incomplete reversal after 4 weeks of abstinence. This underscores the lasting impact of alcohol on oral tissue, even after cessation.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-8"},"PeriodicalIF":1.3,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080806","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

HSYA from safflower mitigates oxidative stress, inflammation, and apoptosis in liver ischemia-reperfusion injury. 红花HSYA减轻肝缺血再灌注损伤的氧化应激、炎症和细胞凋亡。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-05-22 DOI: 10.1080/00498254.2025.2507139

Jianhua Liao, Chunyan Meng, Jun Cheng, Baoqing Liu, Yuzhi Shao

{"title":"HSYA from safflower mitigates oxidative stress, inflammation, and apoptosis in liver ischemia-reperfusion injury.","authors":"Jianhua Liao, Chunyan Meng, Jun Cheng, Baoqing Liu, Yuzhi Shao","doi":"10.1080/00498254.2025.2507139","DOIUrl":"10.1080/00498254.2025.2507139","url":null,"abstract":"Liver ischemia-reperfusion injury (IRI) is a common complication during liver transplantation and surgery, characterised by oxidative stress, inflammation, and apoptosis, which contribute to hepatocyte damage and impaired liver function. Safflower, known for its antioxidant and anti-inflammatory properties, has not been fully explored for its potential to alleviate liver IRI.This study aims to investigate the effects of safflower components on oxidative stress and cell apoptosis in liver IRI. A microfluidic liver cell ischemia-reperfusion model was employed to screen safflower components for their protective effects against oxidative stress and apoptosis. The effects of HSYA and other compounds were assessed by measuring cell viability, ROS levels, apoptosis, DNA damage (8-oxo-dG), lipid peroxidation (MDA), and inflammatory cytokine production (TNF-α, IL-1β, IL-6). HSYA exhibited superior protective effects, significantly reducing ROS, apoptosis, DNA damage, and lipid peroxidation. It also decreased pro-inflammatory cytokine levels, underscoring its antioxidant and anti-inflammatory properties.These findings suggest that HSYA effectively mitigates oxidative stress, inflammation, and apoptosis in liver IRI, positioning it as a promising candidate for therapeutic liver protection.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-7"},"PeriodicalIF":1.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102772","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

Research on LCN2 interference to enhance the sensitivity of drug-resistant strains to gemcitabine. LCN2干扰提高耐药菌株对吉西他滨敏感性的研究。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-05-22 DOI: 10.1080/00498254.2025.2501591

Jianjun Lei, Xuehua Li, Xinpei Wang, Yuwei Xiao, Yang Chi, Qian Sun, He Zhang

{"title":"Research on LCN2 interference to enhance the sensitivity of drug-resistant strains to gemcitabine.","authors":"Jianjun Lei, Xuehua Li, Xinpei Wang, Yuwei Xiao, Yang Chi, Qian Sun, He Zhang","doi":"10.1080/00498254.2025.2501591","DOIUrl":"10.1080/00498254.2025.2501591","url":null,"abstract":"The aim of this study was to observe the sensitivity of the resistant strains to gemcitabine by interfering with the LCN2.An AsPC-1 gemcitabine-resistant cell line (GEM-R) was generated. Based on GEM-R, a lentivirus-infected shRNA-transfected LCN2 cell line was established. The proliferation of LCN2-regulated GEM-R cells was evaluated using the CCK-8 test and the mRNA expression of Ki-67. The apoptosis level of each drug-resistant strain was detected by flow cytometry. The expression of Bax, Bcl-2, Akt, E-cadherin and Vimentin were detected by western blotting.A gemcitabine-resistant strain of AsPC-1 was successfully induced and constructed as an shRNA LCN2 strain based on GEM-R. The interference of LCN2 expression enhanced the tumour inhibition and pro-apoptotic level of gemcitabine, increased the Bax/Bcl-2 value, and decreased p-Akt/Akt value. Meanwhile, the expression of E-cadherin was enhanced while the expression of Vimentin was decreased.This study confirmed that LCN2 affects gemcitabine sensitivity by participating in apoptosis and EMT processes, which may provide potential for overcoming gemcitabine resistance.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-9"},"PeriodicalIF":1.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000415","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

Nano-pharmacokinetics and pharmacodynamics of green-synthesized ZnO nanoparticles: a pathway to safer therapeutic applications. 绿色合成ZnO纳米颗粒的纳米药代动力学和药效学：通往更安全治疗应用的途径。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-05-21 DOI: 10.1080/00498254.2025.2505062

Aishwarya Jain, Kiran Bhise

引用次数: 0

From lab-to-clinic with model informed formulation development: a case study of hydroxyzine SR tablets. 从实验室到临床与模型知情处方开发：羟嗪SR片的案例研究。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-05-21 DOI: 10.1080/00498254.2025.2497045

Aditya Murthy, Shubham Jamdade, Manoj Gundeti, Maddukuri Harika, Rahul Chiliveri, Sangmesh Chaudhari, Veena Kambam, Sohel Khan, Anup Choudhury, Tausif Ahmed

{"title":"From lab-to-clinic with model informed formulation development: a case study of hydroxyzine SR tablets.","authors":"Aditya Murthy, Shubham Jamdade, Manoj Gundeti, Maddukuri Harika, Rahul Chiliveri, Sangmesh Chaudhari, Veena Kambam, Sohel Khan, Anup Choudhury, Tausif Ahmed","doi":"10.1080/00498254.2025.2497045","DOIUrl":"10.1080/00498254.2025.2497045","url":null,"abstract":"Model Informed Formulation Development (MIFD) uses physiologically based pharmacokinetic (PBPK) modelling and other in silico tools to facilitate new product development. These tools help set target profiles, predict in vivo formulation performance, guide iterative development, define dissolution parameters, and convince the regulatory agencies about a drug's safety and efficacy.This study involves development of a sustained release formulation for Hydroxyzine, an anti-histamine with sedation as a significant side effect. The aim was to design a formulation that releases the drug slowly, reducing the peak plasma concentration without losing on the effectiveness. A preliminary absorption model was developed using immediate release formulation data, and various hypothetical dissolution profiles were evaluated in this model. The new drug product, manufactured using MatrixealTM technology, underwent preliminary bioequivalence (BE) studies in healthy volunteers. These results were used to refine the model and further modify the formulation, whose performance was predicted via virtual BE studies. Confirmatory BE studies with 70 volunteers under fasting state validated the new formulation. The model also established clinically relevant dissolution specifications and assessed the food effect on the drug product.This work showcases the application of PBPK modelling in developing new modified release drug product of Hydroxyzine.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-10"},"PeriodicalIF":1.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044770","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

Preclinical pharmacokinetics, metabolism, and disposition of NXE0041178, a novel orally bioavailable agonist of the GPR52 receptor with potential for treatment of schizophrenia and related psychiatric disorders. NXE0041178的临床前药代动力学、代谢和处置，这是一种新型口服GPR52受体激动剂，具有治疗精神分裂症和相关精神疾病的潜力。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-05-19 DOI: 10.1080/00498254.2025.2501593

Simon Poulter, Nigel Austin, Stephen P Watson, Sarah J Bucknell, M Alistair O'Brien, Ari Tolonen, Toni Lassila, Lisa A Stott, Andy Mead, Cliona MacSweeney

{"title":"Preclinical pharmacokinetics, metabolism, and disposition of NXE0041178, a novel orally bioavailable agonist of the GPR52 receptor with potential for treatment of schizophrenia and related psychiatric disorders.","authors":"Simon Poulter, Nigel Austin, Stephen P Watson, Sarah J Bucknell, M Alistair O'Brien, Ari Tolonen, Toni Lassila, Lisa A Stott, Andy Mead, Cliona MacSweeney","doi":"10.1080/00498254.2025.2501593","DOIUrl":"10.1080/00498254.2025.2501593","url":null,"abstract":"The physico-chemical properties, protein binding, metabolism, permeability, transporter interactions, chemical toxicity, and drug-drug interaction potential of the novel GPR52 agonist NXE0041178 were characterised.NXE0041178 demonstrated high cellular permeability, little interaction with efflux transporters P-gp and BCRP, and extensive brain exposure in rodent, consistent with its intended use in CNS disorders.In vivo pharmacokinetic profiling in mouse, rat and monkey demonstrated that NXE0041178 was well-absorbed, with low clearance, a moderate volume-of-distribution and moderate terminal half-life. Oxidative metabolism was the major elimination pathway, with negligible renal or biliary excretion.NXE0041178 displayed good in vitro-to-in vivo correlation in metabolic clearance in preclinical species and low turnover in human in vitro metabolic systems, suggestive of a human pharmacokinetic profile commensurate with once-daily dosing.Early in vitro metabolite identification studies suggested similar metabolic pathways in human and preclinical species, but a distinct metabolic profile in dog.NXE0041178 caused weak heterotropic catalytic activation of CYP3A4, and weak transcriptional induction of CYP3A4 and CYP2B6. No reactive metabolites of NXE0041178 were detected, and no genotoxicity or clinically relevant inhibition of P450 enzymes were observed.These findings extend our knowledge of the preclinical ADME profile of NXE0041178, supporting its continued development.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-16"},"PeriodicalIF":1.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080807","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

LC-MS/MS determination of 27 antipsychotics and metabolites in plasma for medication management monitoring. LC-MS/MS测定血浆中27种抗精神病药物及其代谢物用于用药管理监测。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-05-15 DOI: 10.1080/00498254.2025.2498702

Shanshan Chen, Donghan Wang, Yuanyuan Zhao, Yaqi Sun, Yueyao Luan, Qixuan Sun, Jiaqi Wang, Yuhang Yan, Jing Yu, Chunhua Zhou

{"title":"LC-MS/MS determination of 27 antipsychotics and metabolites in plasma for medication management monitoring.","authors":"Shanshan Chen, Donghan Wang, Yuanyuan Zhao, Yaqi Sun, Yueyao Luan, Qixuan Sun, Jiaqi Wang, Yuhang Yan, Jing Yu, Chunhua Zhou","doi":"10.1080/00498254.2025.2498702","DOIUrl":"10.1080/00498254.2025.2498702","url":null,"abstract":"With the increasing prevalence and escalating complexity of mental disorders, precise medication has become critically important. This necessitates an efficient, accurate, and convenient method for drug concentration monitoring to support laboratory personnel and clinicians. In this study, three liquid chromatography-tandem mass spectrometry methods were developed and validated for simultaneously determining and quantifying 27 antipsychotics and related metabolites in human plasma. The plasma samples were subjected to protein precipitation using methanol, with isotope-labelled internal standards (ISs), followed by separation via isocratic elution on a BEH C18 column. Mass spectrometric analysis was performed using electrospray ionisation in positive ionisation mode with multiple reaction monitoring for quantitative detection. The analytes demonstrated high separation efficiency, with a single sample run time of 3.0 min. The method exhibited a wide linear range with excellent linearity across the concentration range. The intra- and inter-batch precision were ≤10.00%, the accuracy was 88.67-113.29%. Accurate quantification of antipsychotics remained unaffected under various storage conditions: 72 h at room temperature, 7 d at 4 °C refrigeration, and 14 d at -80 °C freezing. This validated methodology has been successfully applied to plasma samples from patients with psychiatric disorders, demonstrating its practical utility for accurate quantification of antipsychotics in large-scale and complex matrices containing multiple analytes.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-14"},"PeriodicalIF":1.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052551","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

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