Xenobiotica最新文献_第9页

Synthesis and evaluation of indomethacin prodrugs with a diester structure that are metabolically activated by human carboxylesterases 合成和评估可被人类羧基酯酶代谢活化的具有二酯结构的吲哚美辛原药

IF 1.8 4区医学

Xenobiotica Pub Date : 2023-12-23 DOI: 10.1080/00498254.2023.2298270

Daisuke Takani, Masato Takahashi, Masakiyo Hosokawa

引用次数: 0

CYP-catalysed Cycling of Clozapine and Clozapine-N-oxide Promotes the Generation of Reactive Oxygen Species in vitro. CYP 催化的氯氮平与氯氮平-N-氧化物的体外循环促进了活性氧的生成。

IF 1.8 4区医学

Xenobiotica Pub Date : 2023-12-18 DOI: 10.1080/00498254.2023.2294473

Ellen Kingston, Malcolm Tingle, Brandi L. Bellissima, Nuala Helsby, Kathryn Burns

引用次数: 0

Through a computer monitor darkly: artificial intelligence in absorption, distribution, metabolism and excretion science. 黑暗中的计算机显示器：吸收、分布、代谢和排泄科学中的人工智能。

IF 1.8 4区医学

Xenobiotica Pub Date : 2023-12-14 DOI: 10.1080/00498254.2023.2295361

Dennis A Smith, Lucy Melanie Burton, Sophie Amanda

引用次数: 0

Effect of Genetic Polymorphisms on the Pharmacokinetics of Gefitinib in Healthy Chinese Volunteers 基因多态性对中国健康志愿者服用吉非替尼的药代动力学的影响

IF 1.8 4区医学

Xenobiotica Pub Date : 2023-12-12 DOI: 10.1080/00498254.2023.2294039

Ying-Rong Chen, Xiang Yu, Li-Min Xu, Jue Mei, Meng-Li Tian, Min Xu, Qiu-Yue Jin, Li-Bing Ye, Shui-Xin Yang

引用次数: 0

Novel application of PBBM to justify impact of faster dissolution on safety and pharmacokinetics – a case study and utility in regulatory justifications 应用 PBBM 来证明快速溶解对安全性和药代动力学影响的新方法--案例研究和在监管论证中的实用性

IF 1.8 4区医学

Xenobiotica Pub Date : 2023-12-07 DOI: 10.1080/00498254.2023.2289160

Rajkumar Boddu, S. Kollipara, Adithya Karthik Bhattiprolu, Tausif Ahmed

引用次数: 0

Effect of berberine on pharmacokinetics and pharmacodynamics of atorvastatin in hyperlipidemia rats. 小檗碱对高脂血症大鼠服用阿托伐他汀的药代动力学和药效学的影响

IF 1.8 4区医学

Xenobiotica Pub Date : 2023-12-01 Epub Date: 2023-12-26 DOI: 10.1080/00498254.2023.2290648

Fan Wu, Mingyu Cui, Siwen Wang, Chao Yu, Weihong Yin, Jiao Li, Xueying Yan

{"title":"Effect of berberine on pharmacokinetics and pharmacodynamics of atorvastatin in hyperlipidemia rats.","authors":"Fan Wu, Mingyu Cui, Siwen Wang, Chao Yu, Weihong Yin, Jiao Li, Xueying Yan","doi":"10.1080/00498254.2023.2290648","DOIUrl":"10.1080/00498254.2023.2290648","url":null,"abstract":"Atorvastatin, an effective lipid-lowering drug, could reduce the risks of morbidity and mortality of cardiovascular diseases. Patients with cardiovascular diseases often use atorvastatin along with berberine. Atorvastatin is the substrate of CYP3A4 and P-gp. However, berberine is the inhibitor. The combination might lead to DDIs. The aim of this study was to assess the effect of berberine on pharmacokinetics and pharmacodynamics of atorvastatin in rats.Plasma concentrations of atorvastatin with or without berberine were determined by HPLC. Pharmacokinetics parameters were calculated and used to evaluate pharmacokinetics interactions. The effect of berberine on pharmacodynamics of atorvastatin was investigated by detecting blood lipid, SOD, MDA, GSH-Px, AST, ALT, and liver histopathology.Cmax, tmax, and AUC0-t of atorvastatin in combination group significantly increased both in normal and model rats (p < 0.01). The increase of t1/2, AUC0-t in model rats was more significant than that in normal rats (p < 0.05). Pharmacodynamics indexes in treatment groups were significantly improved, especially combination group (p < 0.05). Moreover, it could be found that there is a significant recovery in liver histopathology.In conclusion, berberine could affect pharmacokinetics of atorvastatin, enhance lipid-lowering effect and improve liver injury in rats. More attention should be paid to plasma exposure in clinical to avoid adverse reactions.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"644-652"},"PeriodicalIF":1.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138488577","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

Simultaneous determination of four phytoecdysteroids by LC-MS/MS: application to a comparative pharmacokinetic study in normal and adjuvant arthritis rats after oral administration of C. officinalis Kuan phytoecdysteroids extract. 利用 LC-MS/MS 同时测定四种植物十氢类固醇：应用于正常大鼠和佐剂性关节炎大鼠口服川贝母植物十氢类固醇提取物后的药代动力学比较研究。

IF 1.8 4区医学

Xenobiotica Pub Date : 2023-12-01 Epub Date: 2023-12-26 DOI: 10.1080/00498254.2023.2270741

Haiqiang Wang, Deqiang Yang, Shuang Jiang, Yixuan Ren, Lihong Wu, Zhenyue Wang, Haixue Kuang, Zhibin Wang

{"title":"Simultaneous determination of four phytoecdysteroids by LC-MS/MS: application to a comparative pharmacokinetic study in normal and adjuvant arthritis rats after oral administration of C. officinalis Kuan phytoecdysteroids extract.","authors":"Haiqiang Wang, Deqiang Yang, Shuang Jiang, Yixuan Ren, Lihong Wu, Zhenyue Wang, Haixue Kuang, Zhibin Wang","doi":"10.1080/00498254.2023.2270741","DOIUrl":"10.1080/00498254.2023.2270741","url":null,"abstract":"C. officinalis Kuan is the dry root of Cyathula officinalis Kuan. Clinically, it is used for fall and flutter injury, rheumatism and arthralgia. Phytoecdysteroids have significant anti-inflammatory effects, and the phytoecdysteroids present in C. officinalis Kuan exhibit potential for treating rheumatoid arthritis.This study first developed a selective, accurate and efficient LC-MS/MS method for 12-day pharmacokinetic studies regarding the simultaneous determination of cyasterone, 25-epi-28-epi-cyasterone, precyasterone and capitasterone from C. officinalis Kuan phytoecdysteroids extract in normal and adjuvant arthritis rats.An Agilent Eclipse Plus C18 RRHD column (1.8 µm, 50mm × 2.1 mm) with a gradient mobile phase consisting of water (A) and acetonitrile (B) was used for analysis. The mass analysis was performed in an Agilent 6430 QQQ-MS mass spectrometer with positive mode multiple reaction monitoring (MRM).The results indicated that the AUC0-t and AUC0-∞ values of the four phytoecdysteroids in adjuvant arthritis rats were different from those in normal rats on the first day, which could provide a helpful reference for pharmacological and toxicological studies, as well as clinical applications of C. officinalis Kuan in the treatment of rheumatoid arthritis.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"634-643"},"PeriodicalIF":1.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138488578","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

Metabolite profiling and identification of enzymes responsible for the metabolism of hirsutine, a major alkaloid from Uncaria rhynchophylla. 钩藤中主要生物碱多毛素代谢酶的代谢产物分析和鉴定。

IF 1.8 4区医学

Xenobiotica Pub Date : 2023-12-01 Epub Date: 2023-11-03 DOI: 10.1080/00498254.2023.2269417

Yiqing Guo, Huanhuan Lv, Jing Lv, Zenghong Jiang

引用次数: 0

N, N-dimethyltryptamine forms oxygenated metabolites via CYP2D6 - an in vitro investigation. N、 N-二甲基色胺通过CYP2D6形成含氧代谢产物——一项体外研究。

IF 1.8 4区医学

Xenobiotica Pub Date : 2023-12-01 Epub Date: 2023-11-26 DOI: 10.1080/00498254.2023.2278488

Emma Eckernäs, Alicia Macan-Schönleben, Moa Andresen-Bergström, Sofia Birgersson, Kurt-Jürgen Hoffmann, Michael Ashton

{"title":"N, N-dimethyltryptamine forms oxygenated metabolites via CYP2D6 - an in vitro investigation.","authors":"Emma Eckernäs, Alicia Macan-Schönleben, Moa Andresen-Bergström, Sofia Birgersson, Kurt-Jürgen Hoffmann, Michael Ashton","doi":"10.1080/00498254.2023.2278488","DOIUrl":"10.1080/00498254.2023.2278488","url":null,"abstract":"N, N-dimethyltryptamine (DMT) is a psychedelic compound that has shown potential in the treatment of depression. Aside from the primary role of monoamine oxidase A (MAO-A) in DMT metabolism, the metabolic pathways are poorly understood. Increasing this understanding is an essential aspect of ensuring safe and efficacious use of DMT.This work aimed to investigate the cytochrome 450 (CYP) mediated metabolism of DMT by incubating DMT with recombinant human CYP enzymes and human liver microsomes (HLM) followed by analysis using high-resolution mass spectrometry for metabolite identification.DMT was rapidly metabolised by CYP2D6, while stable with all other investigated CYP enzymes. The metabolism of DMT in HLM was reduced after inclusion of harmine and SKF-525A whereas quinidine did not affect the metabolic rate, likely due to MAO-A residues present in HLM. Analysis of the CYP2D6 incubates showed formation of mono-, di- and tri-oxygenated metabolites, likely as a result of hydroxylation on the indole core.More research is needed to investigate the role of this metabolic pathway in vivo and any pharmacological activity of the proposed metabolites. Our findings may impact on safety issues following intake of ayahuasca in slow CYP2D6 metabolizers or with concomitant use of CYP2D6 inhibitors.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"515-522"},"PeriodicalIF":1.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71427436","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

Evobrutinib pathway to its major metabolite M463-2 and insights from a biotransformation and DDI perspective. Evobrutinib通往其主要代谢产物M463-2的途径，以及从生物转化和DDI角度的见解。

IF 1.8 4区医学

Xenobiotica Pub Date : 2023-12-01 Epub Date: 2023-11-26 DOI: 10.1080/00498254.2023.2272180

Holger Scheible, Hanno Schieferstein, Ralf Schmidt, Klaus Pusecker, Ulrike Gradhand, Sathej Gopalakrishnan, Khalid Iqbal, Jennifer Dong, Reinaldo Jones, Claudia Meli, Jayaprakasam Bolleddula, Martin Dyroff, Katrin Georgi

{"title":"Evobrutinib pathway to its major metabolite M463-2 and insights from a biotransformation and DDI perspective.","authors":"Holger Scheible, Hanno Schieferstein, Ralf Schmidt, Klaus Pusecker, Ulrike Gradhand, Sathej Gopalakrishnan, Khalid Iqbal, Jennifer Dong, Reinaldo Jones, Claudia Meli, Jayaprakasam Bolleddula, Martin Dyroff, Katrin Georgi","doi":"10.1080/00498254.2023.2272180","DOIUrl":"10.1080/00498254.2023.2272180","url":null,"abstract":"Evobrutinib is a highly selective, covalent, central nervous system-penetrant Bruton's tyrosine kinase (BTK) inhibitor, currently in Phase III trials for the treatment of relapsing multiple sclerosis. One major circulating metabolite of evobrutinib has been previously identified as the racemic dihydro-diol M463-2 (MSC2430422) in a Phase I human mass balance study.Phenotyping experiments were conducted to confirm the metabolic pathway of evobrutinib to M463-2. Ratio of the enantiomers was determined by enantioselective liquid chromatography with tandem mass spectrometry analysis of plasma samples from humans and preclinical species. Drug-drug interaction (DDI) characterisation, evaluation of pharmacological activity on BTK, and off-target screening experiments followed assessing safety of the metabolite.The biotransformation of evobrutinib to M463-2 was determined to be a two-step process with a CYP-mediated oxidation acting to form an epoxide intermediate, which was further hydrolysed by soluble and mitochondrial epoxide hydrolase. Only the (S)-enantiomer was determined to be a major metabolite, the (R)-enantiomer was minor. In vitro studies demonstrated the (S)-enantiomer lacked clinically relevant pharmacological activity, off-target effects and DDIs.The biotransformation of evobrutinib to its major metabolite has been elucidated, with the major (S)-enantiomer being shown to pose no on/off target or DDI risks.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"547-558"},"PeriodicalIF":1.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50163013","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