Drug Metabolism and Pharmacokinetics最新文献_第4页

How do i build an ‘Ideal’ PBPK model if my drug is either a substrate or inducer 如果我的药物是底物或诱导剂，我如何建立一个“理想的”PBPK模型

IF 2.7 4区医学

Drug Metabolism and Pharmacokinetics Pub Date : 2025-06-01 Epub Date: 2025-06-03 DOI: 10.1016/j.dmpk.2025.101061

Ryuta Asaumi

引用次数: 0

Discovery, validation, and application of transporter endogenous biomarkers: A work of translation 转运体内源性生物标志物的发现、验证和应用：翻译工作

IF 2.7 4区医学

Drug Metabolism and Pharmacokinetics Pub Date : 2025-06-01 Epub Date: 2025-06-03 DOI: 10.1016/j.dmpk.2025.101093

Hong Shen

引用次数: 0

Development of an in vitro Metabolic Dysfunction-Associated Steatohepatitis (MASH) model to study hepatic transporters 建立体外代谢功能障碍相关脂肪性肝炎（MASH）模型研究肝脏转运体

IF 2.7 4区医学

Drug Metabolism and Pharmacokinetics Pub Date : 2025-06-01 Epub Date: 2025-06-03 DOI: 10.1016/j.dmpk.2025.101123

Sarina Kyburz , William A. Murphy , Thomas Kralj , John K. Fallon , Jacqueline B. Tiley , Kim L.R. Brouwer

引用次数: 0

Novel mechanisms of drug-metabolizing hydrolases regulating the toxicity caused by reactive metabolites 药物代谢水解酶调节活性代谢物毒性的新机制

IF 2.7 4区医学

Drug Metabolism and Pharmacokinetics Pub Date : 2025-06-01 Epub Date: 2025-06-03 DOI: 10.1016/j.dmpk.2025.101066

Tatsuki Fukami

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

Drug Metabolism and Pharmacokinetics Pub Date : 2025-06-01 Epub Date: 2025-03-20 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

{"title":"Human aldo-keto reductase (AKR) 1C1 and 1C2 act as coactivators of pregnane X receptor, a master regulator of drug-metabolizing and gluconeogenesis enzymes","authors":"Rei Mitamura , Seiya Takemoto , Yuka Aoyama , Koki Morita , Yuichiro Higuchi , Shotaro Uehara , Nao Yoneda , Hiroshi Suemizu , Tatsuki Fukami , Masataka Nakano , Miki Nakajima","doi":"10.1016/j.dmpk.2025.101481","DOIUrl":"10.1016/j.dmpk.2025.101481","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"62 ","pages":"Article 101481"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144212336","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

Population pharmacokinetics of brexpiprazole in Japanese healthy subjects and patients with schizophrenia brexpiprazole在日本健康人及精神分裂症患者中的群体药代动力学

IF 2.7 4区医学

Drug Metabolism and Pharmacokinetics Pub Date : 2025-06-01 Epub Date: 2025-02-11 DOI: 10.1016/j.dmpk.2025.101057

Koushi Higashi , Tomohiro Sasaki , Kazuo Aoki , Daisuke Sekine , Kenji Maeda , Yuki Shiomi , Yosuke Kawai

{"title":"Population pharmacokinetics of brexpiprazole in Japanese healthy subjects and patients with schizophrenia","authors":"Koushi Higashi , Tomohiro Sasaki , Kazuo Aoki , Daisuke Sekine , Kenji Maeda , Yuki Shiomi , Yosuke Kawai","doi":"10.1016/j.dmpk.2025.101057","DOIUrl":"10.1016/j.dmpk.2025.101057","url":null,"abstract":"<div><div>Brexpiprazole, widely approved for the treatment of schizophrenia, is an atypical antipsychotic that modulates serotonin–dopamine activity. To better understand the pharmacokinetics (PK) of brexpiprazole in Japanese patients, a population PK model was constructed and used to estimate steady state PK profiles and parameters as well as dopamine D<sub>2</sub>/D<sub>3</sub> receptor occupancy profiles after repeated oral administrations of brexpiprazole at 1 and 2 mg/day. Nonlinear mixed effects modelling was used to analyse data from a total of 398 healthy subjects and patients with schizophrenia who received brexpiprazole in three Japanese clinical trials. The PK of brexpiprazole were well described by a two-compartment disposition model with transit absorption compartments. Estimated glomerular filtration rate, age and cytochrome P450 2D6 phenotype were identified as significant covariates on CL/F only. The model predicted that, at a dose of 2 mg/day, trough plasma concentration (90 % prediction interval) of brexpiprazole is 77.1 (22.4–173) ng/mL and that dopamine D<sub>2</sub>/D<sub>3</sub> receptor occupancy is >80 % over one day for most patients at steady state. This suggests the recommended maintenance dose of 2 mg/day of brexpiprazole leads to clinically useful dopamine D<sub>2</sub>/D<sub>3</sub> receptor occupancy at steady state in Japanese patients.</div></div>","PeriodicalId":11298,"journal":{"name":"Drug Metabolism and Pharmacokinetics","volume":"62 ","pages":"Article 101057"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725461","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

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

Drug Metabolism and Pharmacokinetics Pub Date : 2025-06-01 Epub Date: 2025-06-03 DOI: 10.1016/j.dmpk.2025.101149

Murali Subramanian, Deepak Ahire, Rakshit Tanna, Josh Yu, Kelly Wang, Wei Wang, Gillian Smith, Xingrong Liu

引用次数: 0

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

Drug Metabolism and Pharmacokinetics Pub Date : 2025-06-01 Epub Date: 2025-06-03 DOI: 10.1016/j.dmpk.2025.101148

K. Sandy Pang, Weijia Ivy Lu, Gerard Mulder

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

Drug Metabolism and Pharmacokinetics Pub Date : 2025-06-01 Epub Date: 2025-06-03 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

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

Drug Metabolism and Pharmacokinetics Pub Date : 2025-06-01 Epub Date: 2025-06-03 DOI: 10.1016/j.dmpk.2025.101110

Zhu Zhou

引用次数: 0