Evaluation of small interfering RNA-dependent knockdowns of drug-metabolizing enzymes in multiwell array culture of primary human hepatocyte spheroids for estimation of fraction metabolized [0.03%]
基于小发夹RNA干扰的人原代肝细胞球形培养多孔板共培养法评估药物代谢酶对底物化合物表观氯清除率的影响
Lena Brücker,Dominik Jacob,Lena C Preiss et al.
Lena Brücker et al.
The determination of the relative contribution of different drug-metabolizing enzymes to the metabolism of slowly metabolized compounds is a challenging task. The quantification of low compound turnover in standard in vitro systems, such as...
Significance of gut breast cancer resistance protein versus organic anion transporting polypeptide 2B1 inhibition on rosuvastatin clinical drug-drug interactions [0.03%]
肠道乳腺癌耐药蛋白与有机阴离子转运多肽2B1抑制对罗苏伐他汀临床药物相互作用的意义
Mark A West,Sarah Lazzaro,Riley Morrow et al.
Mark A West et al.
Organic anion transporting polypeptide (OATP)2B1 facilitates oral absorption of many drugs including celiprolol, fexofenadine, and rosuvastatin. The present study aimed to examine the relevance of gut OATP2B1 and breast cancer resistance pr...
Prediction of hepatic metabolic clearance in rats and dogs using long-term cocultured hepatocytes [0.03%]
大鼠和狗长期共培养肝细胞预测肝脏代谢清除率
Kenichi Umehara,Florian Klammers,Isabelle Walter et al.
Kenichi Umehara et al.
Knowledge of the accuracy of in vitro to in vivo extrapolation (IVIVE) in preclinical species pharmacokinetics is often used to assess the reliability of physiologically based modeling to predict clinical pharmacokinetics of new chemical en...
In vitro-in vivo scaling of cytochrome P450-mediated metabolic clearance using a relative activity factor approach [0.03%]
采用相对活性因子法进行体外-体内放大的细胞色素P450介导的代谢清除率的研究
Yoko Nagaya,Yoshitane Nozaki
Yoko Nagaya
Quantitative prediction of hepatic clearance is a key element in predicting the human pharmacokinetic profile in the nonclinical stages. In the present study, we focused on the major cytochrome P450 (P450) isoforms (CYP1A2, CYP2C9, CYP2C19,...
Human absorption, distribution, metabolism, and excretion studies: Conventional or microtracer? [0.03%]
人体生物利用度、分布、代谢和排泄的研究：常规研究还是微痕量研究？
Sean Xiaochun Zhu
Sean Xiaochun Zhu
A human absorption, distribution, metabolism, and excretion (hADME) study is an essential clinical pharmacology study for small-molecule drugs. The study provides insights into circulating drug-related materials and the drug's elimination p...
CYP1A2 contributes to the metabolism of mefloquine: Exploration using in vitro metabolism and physiologically-based pharmacokinetic modelling [0.03%]
体外代谢和基于生理的药代动力学模型探索药用化合物细胞色素P450 1A2对奎宁丁代谢的作用
Cleavon K Cloete,Preshendren Govender,Nicholas Njuguna et al.
Cleavon K Cloete et al.
Mefloquine is an antimalarial drug routinely used for prophylaxis and in the treatment of malaria. Approximately 50% of mefloquine metabolism, both in vitro and in vivo, is mediated by CYP3A4 with the remaining contributions by other CYP450...
Novel O-methylpyrimidine prodrugs of phenolic compounds bioactivated by aldehyde oxidase: Enhancing metabolic stability against first-pass conjugative metabolism in the intestine [0.03%]
由醛氧化酶生物活化的酚类化合物的新O-甲基哒嗪前药：增强肠道一过性共轭代谢的代谢稳定性
John P Kowalski,Brian R Baer,Samuel D Randall et al.
John P Kowalski et al.
Phenol-containing drugs may exhibit limited oral bioavailability due to first-pass conjugation in the intestine and liver, and potentially unfavorable biopharmaceutical properties imparted by the hydrogen-bond donor. We present a novel prod...
Switch/sucrose non-fermentable complex interacts with constitutive androstane receptor to regulate drug-metabolizing enzymes and transporters in the liver [0.03%]
开关/蔗糖不发酵复合物与雄烷基受体相互作用以调节肝脏中的药物代谢酶和转运蛋白
Kiamu Kurosawa,Masataka Nakano,Itsuki Yokoseki et al.
Kiamu Kurosawa et al.
Constitutive androstane receptor (CAR) is a nuclear receptor that plays an important role in regulating drug metabolism and bile acid homeostasis in the liver. Recently, it was revealed that the switch/sucrose non-fermentable (SWI/SNF) comp...
Development of human embryonic stem cell-derived cardiomyocytes and application of fluorescence probe substrate for characterization of cytochrome P450 enzyme 2J2 [0.03%]
人胚胎干细胞衍生的心肌细胞的发育及荧光探针底物在细胞色素P450酶2J2特性分析中的应用
Xingyu Zhu,Yee Kiat Soh,Mingxin Wan et al.
Xingyu Zhu et al.
Cardiac cytochrome P450 2J2 (CYP2J2) plays a significant role in cardiovascular homeostasis due to its dual functions in drug metabolism and the epoxidation of polyunsaturated fatty acids. Additionally, the inhibition of CYP2J2 by xenobioti...