Use of Segregated Hepatocyte Scaling Factors and Cross-Species Relationships to Resolve Clearance Dependence in the Prediction of Human Hepatic Clearance [0.03%]
使用分离肝细胞放大因子和跨物种关系来解决预测人的肝脏清除率时的依赖性问题
D Hallifax,J B Houston
D Hallifax
Human and rat hepatocytes have a strong tendency to underpredict hepatic intrinsic clearance (CLint) and the extent of underprediction increases with increasing observed CLint In this study, application of the log average rat hepatocyte-rat...
Continuum of Host-Gut Microbial Co-metabolism: Host CYP3A4/3A7 are Responsible for Tertiary Oxidations of Deoxycholate Species [0.03%]
主客体共生代谢连续谱：宿主CYP3A4/3A7负责脱氧胆酸三元氧化反应
Jian Zhang,Ling-Zhi Gao,Yu-Jie Chen et al.
Jian Zhang et al.
The gut microbiota modifies endogenous primary bile acids (BAs) to produce exogenous secondary BAs, which may be further metabolized by cytochrome P450 enzymes (P450s). Our primary aim was to examine how the host adapts to the stress of mic...
The MBNL/CELF Splicing Factors Regulate Cytosolic Sulfotransferase 4A1 Protein Expression during Cell Differentiation [0.03%]
MBNL / CELF剪接因子在细胞分化过程中调节胞质硫酸转移酶4A1蛋白表达
Misgana Idris,Neville J Butcher,Rodney F Minchin
Misgana Idris
Sulfotransferase 4A1 (SULT4A1) is a sulfotransferase-like protein that is highly conserved between species. In human tissues, there are two transcripts, one that produces a full-length protein and one that produces an unstable truncated pro...
Breast Cancer Resistance Protein and Multidrug Resistance Protein 2 Determine the Disposition of Esculetin-7-O-Glucuronide and 4-Methylesculetin-7-O-Glucuronide [0.03%]
白蛋白和MRP2决定Esculetin-7-O-glucuronide和4-Methylesculetin-7-O-glucuronide的分布
Yuhuan Li,Wenjie Song,Xiaojun Ou et al.
Yuhuan Li et al.
Esculetin (ET)-7-O-glucuronide (ET-G) and 4-methylesculetin (4-ME)-7-O-glucuronide (4-ME-G) are the main glucuronide of ET and 4-ME, respectively. The disposition mediated by efflux transporters for glucuronide has significant influence on ...
Commensal Gut Bacteria Convert the Immunosuppressant Tacrolimus to Less Potent Metabolites [0.03%]
肠道共生细菌将免疫抑制剂他克莫司转化为活性较低的代谢物
Yukuang Guo,Camila Manoel Crnkovic,Kyoung-Jae Won et al.
Yukuang Guo et al.
Tacrolimus exhibits low and variable drug exposure after oral dosing, but the contributing factors remain unclear. Based on our recent report showing a positive correlation between fecal abundance of Faecalibacterium prausnitzii and oral ta...
In Silico Prediction of the Absorption and Disposition of Cefadroxil in Humans using an Intestinal Permeability Method Scaled from Humanized PepT1 Mice [0.03%]
基于人源化PepT1小鼠外推的肠通透性方法预测头孢泊肟在人体内的吸收和分布特性
Yongjun Hu,David E Smith
Yongjun Hu
It is difficult to predict the pharmacokinetics and plasma concentration-time profiles of new chemical entities in humans based on animal data. Some pharmacokinetic parameters, such as clearance and volume of distribution, can be scaled all...
Hepatic Organic Anion Transporting Polypeptide-Mediated Clearance in the Beagle Dog: Assessing In Vitro-In Vivo Relationships and Applying Cross-Species Empirical Scaling Factors to Improve Prediction of Human Clearance [0.03%]
以比格犬为对象研究肝有机阴离子转运多肽介导的清除：评估体外-体内关系，并运用跨物种经验缩放因子改善对人类清除率的预测
Norikazu Matsunaga,Ayşe Ufuk,Bridget L Morse et al.
Norikazu Matsunaga et al.
In the present study, the beagle dog was evaluated as a preclinical model to investigate organic anion transporting polypeptide (OATP)-mediated hepatic clearance. In vitro studies were performed with nine OATP substrates in three lots of pl...
Regulation of Hepatic Long Noncoding RNAs by Pregnane X Receptor and Constitutive Androstane Receptor Agonists in Mouse Liver [0.03%]
孕烷X受体和构象雄甾烷受体激动剂对小鼠肝脏长链非编码RNA的调控作用
Joseph L Dempsey,Julia Yue Cui
Joseph L Dempsey
Altered expression of long noncoding RNAs (lncRNAs) by environmental chemicals modulates the expression of xenobiotic biotransformation-related genes and may serve as therapeutic targets and novel biomarkers of exposure. The pregnane X rece...
A Recombinant Humanized Anticocaine Monoclonal Antibody Alters the Urinary Clearance of Cocaine and Its Metabolites in Rats [0.03%]
一种重组人源化抗可卡因单克隆抗体可改变大鼠尿液中可卡因及其代谢产物的排泄速率
Jordan A Marckel,Hanna N Wetzel,Sihame Amlal et al.
Jordan A Marckel et al.
A recombinant humanized anticocaine monoclonal antibody, h2E2, has shown potential in the preclinical phases for the treatment of cocaine abuse. The standard tests for cocaine usage are the detection of benzoylecgonine (BE) and cocaine in t...
Suppression of Hepatic CYP3A4 Expression and Activity by 3-Methylcholanthrene in Humanized PXR-CAR-CYP3A4/3A7 Mice [0.03%]
3-甲基胆烷烯酚酮通过人源化PXR-CAR-CYP3A4/3A7小鼠抑制肝CYP3A4的表达和代谢功能
Michael Crosby,David S Riddick
Michael Crosby
Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants that activate the aryl hydrocarbon receptor, thereby triggering a range of biologic responses, exemplified by the induction of CYP1A1 PAHs can also regulate the expression...