Cytochrome P450 inhibition correlates with hepatotoxicity of pesticides: Analysis using repeated-dose toxicity data in rats [0.03%]
细胞色素P450抑制与农药肝毒性相关性分析：基于大鼠重复剂量毒性数据的研究
Minami Shibata,Nana Uchida,Akira Ooka et al.
Minami Shibata et al.
Drug-induced liver injury (DILI) remains a significant challenge in drug development and safety assessment, requiring a deeper understanding of its underlying mechanisms. We recently reported that the inhibition of cytochrome P450 (P450) en...
Analysis of blood-brain barrier permeability of drugs using forensically obtained human cerebrospinal fluid and plasma in Japan [0.03%]
利用日本法医获得的人体脑脊液和血浆分析药物的血脑屏障通透性
Tomoyoshi Hariba,Kenta Mizoi,Saori Takahashi et al.
Tomoyoshi Hariba et al.
Distribution coefficient the cerebrospinal fluid (CSF) concentration ratios of unbound drugs to serum (Ks,uu,CSF) were calculated from drugs detected in serum and CSF obtained at forensic autopsies in Japan, and documented values of serum p...
A novel quantitative assessment of formed reactive metabolites by double trapping with [3H]glutathione and [14C]cyanide [0.03%]
一种新的定量评估方法：通过与[3H]谷胱甘肽和[14C]氰化物双重结合来形成反应性代谢产物的新定量评估方法
Tomoyuki Kawachi,Tatsuki Fukami,Miki Nakajima
Tomoyuki Kawachi
Drug-induced liver injury often arises from reactive metabolites (RMs) produced in the liver, making it crucial to assess RM formation rates from drug candidates. Conventional assays using glutathione (GSH) effectively trap soft electrophil...
Metabolism of simvastatin by Streptomyces griseolus CYP105A1 and its variants for the production of human simvastatin metabolites [0.03%]
灰色链霉菌CYP105A1及其变异体代谢辛伐他汀产生人类辛伐他汀代谢物
Sachiyo Yoneda,Kaori Yasuda,Bunzo Mikami et al.
Sachiyo Yoneda et al.
Streptomyces griseolus CYP105A1 showed hydroxylation activity at 25- and 1α-positions of vitamin D3 to produce an active form of vitamin D3. We have succeeded in dramatically increasing its activity by site-directed mutagenesis. We also fo...
Important role of OATP in the liver disposition of ezetimibe and its consequent glucuronidation metabolite [0.03%]
有机阴离子转运多肽在肝脏中调节依折麦布及其葡糖醛酸结合代谢产物 disposition 中的重要作用
Ying Su,Xinyi Zhang,Yiguo Jiang et al.
Ying Su et al.
Ezetimibe is a widely used antilipemic agent that lowers LDL-C and raises HDL-C by inhibiting intestinal cholesterol absorption. However, the mechanisms governing the hepatic transport of ezetimibe and its glucuronide metabolite remain uncl...
L-Type amino acid transporter 1-mediated developmental change of cerebral gabapentin distribution across the rat blood-brain barrier [0.03%]
血脑屏障中利诺氨转运体1介导的脑佩尼卡明发育性变化分布于大鼠中
Hiroki Endo,Takeshi Sugouchi,Otaro Kobayashi et al.
Hiroki Endo et al.
Gabapentin is an anticonvulsant used in the pharmacotherapy of pediatric epilepsy. Differences in transporter-mediated cerebral drug/compound distribution across the blood-brain barrier (BBB) have been reported between neonates/infants, and...
Tyrosine kinase inhibitors, nilotinib and radotinib, suppress both catalytic function and mRNA expression of human cytochrome P450 2J2 and 2C8 [0.03%]
酪氨酸激酶抑制剂尼洛替尼和拉多替尼可同时抑制人类细胞色素P450 2J2和2C8的催化功能及mRNA表达
Ayaka Kojima,Masayuki Nadai,Hiroshi Yamazaki et al.
Ayaka Kojima et al.
Cytochrome P450 (P450 or CYP) 2J2, which metabolizes exogenous medicines and endogenous arachidonic acid to 14,15-epoxyeicosatrienoic acid (14,15-EET), is expressed in various organs and cancer cells. Additionally, CYP2C8 catalyzes the synt...
Impact of degradation in subcutaneous tissue and lymphatic fluid on absorption of Fc-fusion proteins following subcutaneous administration [0.03%]
皮下组织退化和淋巴液对Fc融合蛋白皮下给药吸收的影响
Miki Yokoyama,Eiko Suzuki,Daisuke Nakai
Miki Yokoyama
Subcutaneous administration is widely used as a clinical administration route for Fc-fusion proteins. However, predicting bioavailability (BA) in humans after subcutaneous administration is challenging due to multiple factors involved in th...
Construction of refined CYP2D6-Template system for studies of its metabolism and inhibition [0.03%]
用于研究CYP2D6代谢和抑制作用的精制CYP2D6模板系统的构建
Yasushi Yamazoe,Norie Murayama,Kouichi Yoshinari
Yasushi Yamazoe
The previously reported Template system for the prediction of human CYP2D6-mediated reactions (Drug Metab Dispos 40 486-96, 2012) has been refined with the introduction of ideas of allowable width, Trigger∗-residue and the residue-initiate...
Japanese medicinal drug labeling for use in the clinical setting as informed by pharmacogenomic data on cytochrome P450 enzymes obtained from in silico studies [0.03%]
基于体外研究获得的细胞色素P450酶药物基因组数据在临床用药环境中的日本药品说明书修订
Yoichi Tanaka,Makiko Shimizu,Yoshiro Saito et al.
Yoichi Tanaka et al.
Although the United States Food and Drug Administration has disclosed a list of drugs with pharmacogenomic biomarkers for drug labeling, there is limited information regarding pharmacogenomic-associated drugs in Japan. Such associations inc...