Elizabeth A Hausner,Susan A Elmore,Xi Yang
Elizabeth A Hausner
Metabolism in organs other than the liver and kidneys may play a significant role in how a specific organ responds to chemicals. The heart has metabolic capability for energy production and homeostasis. This homeostatic machinery can also p...
Mechanism of Reductive Metabolism and Chiral Inversion of Proton Pump Inhibitors [0.03%]
proton pump抑制剂还原代谢和手性反转的机制研究
Chongzhuang Tang,Zhaoqiang Chen,Xiaojian Dai et al.
Chongzhuang Tang et al.
Racemic proton pump inhibitors (PPIs) have been developed into pure enantiomers given superior pharmacokinetic profiles. However, after doses of single enantiomer PPIs, different degrees of chiral inversion were observed. We investigated th...
Modeling of Hepatic Drug Metabolism and Responses in CYP2C19 Poor Metabolizer Using Genetically Manipulated Human iPS cells [0.03%]
基于遗传调控的人诱导多能干细胞的肝药代谢及反应机制构建研究（以贫代谢酶型CYP2C19为例）
Sayaka Deguchi,Tomoki Yamashita,Keisuke Igai et al.
Sayaka Deguchi et al.
Cytochrome P450 family 2 subfamily C member 19 (CYP2C19), in liver, plays important roles in terms of drug metabolism. It is known that CYP2C19 poor metabolizers (PMs) lack CYP2C19 metabolic capacity. Thus, unexpected drug-induced liver inj...
Sarah M Glass,Sabrina M Leddy,Michael C Orwin et al.
Sarah M Glass et al.
Rolapitant [(Varubi), 5S,8S)-8-[[(1R)-1-[3,5 bis(trifluoromethyl phenyl]ethoxy]methyl]-8-phenyl-1,7-diazaspiro[4.5]decan-2-one] is a high-affinity NK1 receptor antagonist that was approved in September 2015 as a treatment for nausea and vom...
Prediction of Human Nonlinear Pharmacokinetics of a New Bcl-2 Inhibitor Using PBPK Modeling and Interspecies Extrapolation Strategy [0.03%]
基于PBPK模型和种间外推策略预测新的Bcl-2抑制剂在人体内的非线性药代动力学性质
Philippe B Pierrillas,Emilie Henin,Kathryn Ball et al.
Philippe B Pierrillas et al.
S 55746 ((S)-N-(4-hydroxyphenyl)-3-(6-(3-(morpholinomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzo[d][1,3]dioxol-5-yl)-N-phenyl-5,6,7,8-tetrahydroindolizine-1-carboxamide) is a new selective Bcl-2 (B-cell lymphoma 2) inhibitor deve...
Impairment of Intestinal Monocarboxylate Transporter 6 Function and Expression in Diabetic Rats Induced by Combination of High-Fat Diet and Low Dose of Streptozocin: Involvement of Butyrate-Peroxisome Proliferator-Activated Receptor- γ Activation [0.03%]
高脂饮食与低剂量链脲佐菌素联合诱导的糖尿病大鼠肠道单羧酸转运蛋白6功能和表达障碍：涉及丁酸-过氧化物酶体增殖激活受体γ途径
Feng Xu,Liang Zhu,Chaoqun Qian et al.
Feng Xu et al.
Generally, diabetes remarkably alters the expression and function of intestinal drug transporters. Nateglinide and bumetanide are substrates of monocarboxylate transporter 6 (MCT6). We investigated whether diabetes down-regulated the functi...
Stereoselective Oxidation Kinetics of Deoxycholate in Recombinant and Microsomal CYP3A Enzymes: Deoxycholate 19-Hydroxylation Is an In Vitro Marker of CYP3A7 Activity [0.03%]
脱氧胆汁酸在重组和微粒体CYP3A酶中的立体选择性氧化动力学：脱氧胆汁酸19-羟基化是CYP3A7活性的体外标志物
Yu-Jie Chen,Jian Zhang,Ping-Ping Zhu et al.
Yu-Jie Chen et al.
The primary bile acids (BAs) synthesized from cholesterol in the liver are converted to secondary BAs by gut microbiota. It was recently disclosed that the major secondary BA, deoxycholate (DCA) species, is stereoselectively oxidized to ter...
Maternal Plasma l-Carnitine Reduction During Pregnancy Is Mainly Attributed to OCTN2-Mediated Placental Uptake and Does Not Result in Maternal Hepatic Fatty Acid β-Oxidation Decline [0.03%]
母体血浆左旋肉碱在妊娠期的降低主要归因于OCTN2介导的胎盘摄取，并未导致母体肝脏β-氧化下降
Mengru Bai,Qingquan Zeng,Yingchun Chen et al.
Mengru Bai et al.
l-Carnitine (l-Car) plays a crucial role in fatty acid β-oxidation. However, the plasma l-Car concentration in women markedly declines during pregnancy, but the underlying mechanism and its consequences on maternal hepatic β-oxidation hav...
An Extensively Humanized Mouse Model to Predict Pathways of Drug Disposition and Drug/Drug Interactions, and to Facilitate Design of Clinical Trials [0.03%]
一种预测药物处置及药物/药物相互作用的广泛人类化小鼠模型，并有助于临床试验的设计
C J Henderson,Y Kapelyukh,N Scheer et al.
C J Henderson et al.
Species differences in drug metabolism and disposition can confound the extrapolation of in vivo PK data to man and also profoundly compromise drug efficacy studies owing to differences in pharmacokinetics, in metabolites produced (which ar...
Intracellular and Intraorgan Concentrations of Small Molecule Drugs: Theory, Uncertainties in Infectious Diseases and Oncology, and Promise [0.03%]
小分子药物的细胞内及器官内的浓度：理论、传染病和肿瘤学中的不确定性以及其前景
Dennis A Smith,Malcolm Rowland
Dennis A Smith
The distribution of a drug within the body should be considered as involving movement of unbound drug between the various aqueous spaces of the body. At true steady state, even for a compound of restricted lipoidal permeability, unbound con...