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Drug Metabolism and Pharmacokinetics最新文献

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Selection of liver models of hepatic drug clearance: Improvements and implications for ivive and PBPK modeling 肝脏药物清除模型的选择：活体和PBPK模型的改进和意义
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Drug Metabolism and Pharmacokinetics
Pub Date : 2025-06-01 DOI: 10.1016/j.dmpk.2025.101148
K. Sandy Pang, Weijia Ivy Lu, Gerard Mulder
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引用次数: 0
Intestinal secretion is potentially an important clearance mechanism for highly plasma-bound and low metabolic clearance efflux substrates 肠道分泌可能是高血浆结合和低代谢清除外排底物的重要清除机制
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Drug Metabolism and Pharmacokinetics
Pub Date : 2025-06-01 DOI: 10.1016/j.dmpk.2025.101149
Murali Subramanian, Deepak Ahire, Rakshit Tanna, Josh Yu, Kelly Wang, Wei Wang, Gillian Smith, Xingrong Liu
{"title":"Intestinal secretion is potentially an important clearance mechanism for highly plasma-bound and low metabolic clearance efflux substrates","authors":"Murali Subramanian, Deepak Ahire, Rakshit Tanna, Josh Yu, Kelly Wang, Wei Wang, Gillian Smith, Xingrong Liu","doi":"10.1016/j.dmpk.2025.101149","DOIUrl":"10.1016/j.dmpk.2025.101149","url":null,"abstract":"","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"61 ","pages":"Article 101149"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144194500","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
Identification of physiological factors suppressing colonic drug absorption using quantum imaging technology 利用量子成像技术鉴定抑制结肠药物吸收的生理因素
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Drug Metabolism and Pharmacokinetics
Pub Date : 2025-06-01 DOI: 10.1016/j.dmpk.2025.101141
Yugo Yasugi , Maho Hirosaki , Kazuki Hotta , Yumi Kato , Yasuyuki Ueda , Mayumi Iwatake , Hiroshi Yukawa , Ikumi Tamai , Yoshiyuki Shirasaka
{"title":"Identification of physiological factors suppressing colonic drug absorption using quantum imaging technology","authors":"Yugo Yasugi , Maho Hirosaki , Kazuki Hotta , Yumi Kato , Yasuyuki Ueda , Mayumi Iwatake , Hiroshi Yukawa , Ikumi Tamai , Yoshiyuki Shirasaka","doi":"10.1016/j.dmpk.2025.101141","DOIUrl":"10.1016/j.dmpk.2025.101141","url":null,"abstract":"","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"61 ","pages":"Article 101141"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144194590","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
Mitigating strategy for drug induced liver injury LED by reactive metabolites 反应性代谢物对药物性肝损伤的缓解策略
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Drug Metabolism and Pharmacokinetics
Pub Date : 2025-06-01 DOI: 10.1016/j.dmpk.2025.101065
Sean Zhu
{"title":"Mitigating strategy for drug induced liver injury LED by reactive metabolites","authors":"Sean Zhu","doi":"10.1016/j.dmpk.2025.101065","DOIUrl":"10.1016/j.dmpk.2025.101065","url":null,"abstract":"","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"61 ","pages":"Article 101065"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144194660","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
Unraveling cannabinoids-drug interactions in aging: Insights from PBPK modeling 揭示大麻素-药物在衰老中的相互作用：来自PBPK模型的见解
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Drug Metabolism and Pharmacokinetics
Pub Date : 2025-06-01 DOI: 10.1016/j.dmpk.2025.101110
Zhu Zhou
{"title":"Unraveling cannabinoids-drug interactions in aging: Insights from PBPK modeling","authors":"Zhu Zhou","doi":"10.1016/j.dmpk.2025.101110","DOIUrl":"10.1016/j.dmpk.2025.101110","url":null,"abstract":"","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"61 ","pages":"Article 101110"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144194669","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
TOC TOC
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Drug Metabolism and Pharmacokinetics
Pub Date : 2025-06-01 DOI: 10.1016/S1347-4367(25)00438-0
{"title":"TOC","authors":"","doi":"10.1016/S1347-4367(25)00438-0","DOIUrl":"10.1016/S1347-4367(25)00438-0","url":null,"abstract":"","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"61 ","pages":"Article 101488"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144195346","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
Gastrointestinal imaging with MRI: Insights into the behavior of dosage forms and the conditions at the site of drug release 胃肠道成像与MRI：洞察剂量形式的行为和药物释放部位的条件
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Drug Metabolism and Pharmacokinetics
Pub Date : 2025-06-01 DOI: 10.1016/j.dmpk.2025.101069
Werner Weitschies
{"title":"Gastrointestinal imaging with MRI: Insights into the behavior of dosage forms and the conditions at the site of drug release","authors":"Werner Weitschies","doi":"10.1016/j.dmpk.2025.101069","DOIUrl":"10.1016/j.dmpk.2025.101069","url":null,"abstract":"","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"61 ","pages":"Article 101069"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144195400","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
Human aldo-keto reductase (AKR) 1C1 and 1C2 act as coactivators of pregnane X receptor, a master regulator of drug-metabolizing and gluconeogenesis enzymes 人醛酮还原酶（AKR） 1C1和1C2是孕激素X受体的共激活因子，是药物代谢和糖异生酶的主要调节因子
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Drug Metabolism and Pharmacokinetics
Pub Date : 2025-06-01 DOI: 10.1016/j.dmpk.2025.101481
Rei Mitamura , Seiya Takemoto , Yuka Aoyama , Koki Morita , Yuichiro Higuchi , Shotaro Uehara , Nao Yoneda , Hiroshi Suemizu , Tatsuki Fukami , Masataka Nakano , Miki Nakajima
The aldo-keto reductase (AKR) 1C subfamily, comprising AKR1C1-1C4, plays a crucial role in drug metabolism and hormone biosynthesis. Recent studies have identified AKR1C3 as a co-activator of the androgen receptor. This study aimed to investigate whether AKR1Cs function as regulators of the pregnane X receptor (PXR), a member of the nuclear receptor superfamily, which upregulates drug-metabolizing enzymes such as cytochrome P450 (CYP) 3A4. Rifampicin-activated CYP3A4 induction was attenuated by AKR1C1/1C2 knockdown in ShP51 cells (PXR-overexpressing HepG2 cells), HepaRG cells, and HepaSH cells (hepatocytes from humanized liver mice). Co-immunoprecipitation analysis revealed that AKR1Cs interact with PXR. Immunofluorescent staining revealed that AKR1Cs are translocated into the nucleus with PXR by rifampicin in HepaRG cells. These results suggested that AKR1C1/1C2 has an ability to enhance transactivity of PXR. Consistent with the results of knockdown experiments, PXR-mediated CYP3A4 induction was significantly attenuated by treatment with AKR1C1/1C2 inhibitors, diazepam or flunitrazepam, in ShP51, HepaRG, and HepaSH cells. Furthermore, the induction of CYP2B6, CYP2C9, glucose 6-phosphatase, and phosphoenolpyruvate carboxykinase 1, all regulated by PXR, was attenuated by AKR1C1/1C2 inhibitors. Collectively, we demonstrated that AKR1C1/1C2 upregulates PXR transactivation. Clinically used drugs that inhibit AKR1C1/1C2 may suppress PXR-mediated transactivation of genes encoding drug-metabolizing and gluconeogenesis enzymes.
醛酮还原酶（AKR） 1C亚家族包括AKR1C1-1C4，在药物代谢和激素生物合成中起重要作用。最近的研究已经确定AKR1C3是雄激素受体的共激活剂。本研究旨在研究AKR1Cs是否作为妊娠X受体（PXR）的调节因子，PXR是核受体超家族的成员，可上调细胞色素P450 (CYP) 3A4等药物代谢酶。在ShP51细胞（pxr过表达HepG2细胞）、HepaRG细胞和HepaSH细胞（人源化肝小鼠的肝细胞）中，akr11.1 / 1c2敲低可减弱利福平激活的CYP3A4诱导。共免疫沉淀分析显示akr1c与PXR相互作用。免疫荧光染色显示，在HepaRG细胞中，akr1c通过利福平与PXR一起易位到细胞核中。这些结果表明，akr11.1 / 1c2具有增强PXR交互活性的能力。与敲低实验结果一致，在ShP51、HepaRG和HepaSH细胞中，使用akr11.1 / 1c2抑制剂地西泮或氟硝西泮治疗后，pxr介导的CYP3A4诱导显著减弱。此外，由PXR调控的CYP2B6、CYP2C9、葡萄糖6-磷酸酶和磷酸烯醇丙酮酸羧激酶1的诱导作用被akr11.1 / 1c2抑制剂减弱。总的来说，我们证明了akr11.1 / 1c2上调PXR的转录激活。临床使用的抑制akr11.1 / 1c2的药物可能会抑制pxr介导的药物代谢和糖异生酶编码基因的转激活。
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引用次数: 0
Advances in enabling IVIVE and enzyme phenotyping of low clearance compounds 低清除率化合物的激活IVIVE和酶表型研究进展
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Drug Metabolism and Pharmacokinetics
Pub Date : 2025-06-01 DOI: 10.1016/j.dmpk.2025.101103
Mitesh Patel
{"title":"Advances in enabling IVIVE and enzyme phenotyping of low clearance compounds","authors":"Mitesh Patel","doi":"10.1016/j.dmpk.2025.101103","DOIUrl":"10.1016/j.dmpk.2025.101103","url":null,"abstract":"","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"61 ","pages":"Article 101103"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144195546","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
Enhanced effect of ionic liquid on intestinal absorption of macromolecules (< 10 kDa) 离子液体对肠道大分子（< 10 kDa）吸收的促进作用
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Drug Metabolism and Pharmacokinetics
Pub Date : 2025-06-01 DOI: 10.1016/j.dmpk.2025.101137
Shoichiro Fukuda , Haruka Takata , Takashi Nakae , Noboru Tatsumi , Hidetoshi Hamamoto , Hidenori Ando , Tatsuhiro Ishida
{"title":"Enhanced effect of ionic liquid on intestinal absorption of macromolecules (< 10 kDa)","authors":"Shoichiro Fukuda ,&nbsp;Haruka Takata ,&nbsp;Takashi Nakae ,&nbsp;Noboru Tatsumi ,&nbsp;Hidetoshi Hamamoto ,&nbsp;Hidenori Ando ,&nbsp;Tatsuhiro Ishida","doi":"10.1016/j.dmpk.2025.101137","DOIUrl":"10.1016/j.dmpk.2025.101137","url":null,"abstract":"","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"61 ","pages":"Article 101137"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144195589","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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