Fraction Unbound for Liver Microsome and Hepatocyte Incubations for All Major Species Can Be Approximated Using a Single-Species Surrogate [0.03%]
所有主要物种的肝微粒体和肝细胞孵育的分数未结合可以使用单物种替代物进行近似估算
John T Barr,Julie M Lade,Thuy B Tran et al.
John T Barr et al.
It is well recognized that nonspecific binding of a drug within an in vitro assay (f u) can have a large impact on in vitro to in vivo correlations of intrinsic clearance. Typically, this value is determined experimentally across multiple s...
Critical Differences between Enzyme Sources in Sensitivity to Detect Time-Dependent Inactivation of CYP2C8 [0.03%]
不同酶来源对检测CYP2C8时间依赖性失活敏感度差异的影响分析
Helinä Kahma,Anne M Filppula,Terhi Launiainen et al.
Helinä Kahma et al.
Clopidogrel acyl-β-d-glucuronide is a mechanism-based inhibitor of cytochrome P450 2C8 in human liver microsomes (HLMs). However, time-dependent inactivation (TDI) of CYP2C8 could not be detected in an earlier study in human recombinant CY...
Brain Distribution of a Panel of Epidermal Growth Factor Receptor Inhibitors Using Cassette Dosing in Wild-Type and Abcb1/Abcg2-Deficient Mice [0.03%]
一组表皮生长因子受体抑制剂在野生型和ABCB1/ABCG2缺陷小鼠中的脑分布：剂量集翻译结果表明
Minjee Kim,Janice K Laramy,Afroz S Mohammad et al.
Minjee Kim et al.
Tyrosine kinase inhibitors that target the epidermal growth factor receptor (EGFR) have had success in treating EGFR-positive tumors, including non-small-cell lung cancer (NSCLC). However, developing EGFR inhibitors that can be delivered to...
In Vitro-In Vivo Extrapolation of Key Transporter Activity at the Blood-Brain Barrier [0.03%]
体外-体内推算血脑屏障关键转运蛋白活性
Patrick E Trapa,Matthew D Troutman,Thomas Y Lau et al.
Patrick E Trapa et al.
Understanding the quantitative implications of P-glycoprotein and breast cancer resistance protein efflux is a key hurdle in the design of effective, centrally acting or centrally restricted therapeutics. Previously, a comprehensive physiol...
Induction of Cytochrome P450 Involved in the Accelerated Blood Clearance Phenomenon Induced by PEGylated Liposomes In Vivo [0.03%]
体内聚乙二醇化脂质体诱导加速血液清除现象的细胞色素P450的诱导作用
Fengling Wang,Yifan Wu,Jiwen Zhang et al.
Fengling Wang et al.
Polyethylene glycol (PEG) is recognized as an attractive excipient to modify liposomes due to its extended-circulation properties. Nevertheless, intravenous injection of polyethylene glycol-coated liposomes (PEG-L) usually triggers a rapid ...
The Presence of a Transporter-Induced Protein Binding Shift: A New Explanation for Protein-Facilitated Uptake and Improvement for In Vitro-In Vivo Extrapolation [0.03%]
关于转运蛋白诱导的蛋白质结合位移的存在：一种新的体内体外相互作用解释及改善蛋白质摄取促进的新观点
Christine M Bowman,Hideaki Okochi,Leslie Z Benet
Christine M Bowman
Accurately predicting hepatic clearance is an integral part of the drug-development process, and yet current in vitro to in vivo (IVIVE) extrapolation methods yield poor predictions, particularly for highly protein-bound transporter substra...
Hepatocyte Concentrations of Imaging Compounds Associated with Transporter Inhibition: Evidence in Perfused Rat Livers [0.03%]
基于转运体抑制的影像剂在灌流大鼠肝脏内的肝细胞浓度分布研究
Pierre Bonnaventure,Fabien Cusin,Catherine M Pastor
Pierre Bonnaventure
In the liver, several approaches are used to investigate and predict the complex issue of drug-induced transporter inhibition. These approaches include in vitro assays and pharmacokinetic models that predict how inhibitors modify the system...
Clopidogrel and Gemfibrozil Strongly Inhibit the CYP2C8-Dependent Formation of 3-Hydroxydesloratadine and Increase Desloratadine Exposure In Humans [0.03%]
氯吡格雷和吉非罗齐通过抑制CYP2C8显著增加左旋克洛替丁的血药浓度
Matti K Itkonen,Aleksi Tornio,Mikko Neuvonen et al.
Matti K Itkonen et al.
A recent in vitro study suggested that CYP2C8 is essential in the metabolism of desloratadine, an H1 receptor antagonist. If the proposed biotransformation mechanism takes place in vivo in humans, desloratadine could serve as a selective CY...
A Comparison of Total and Plasma Membrane Abundance of Transporters in Suspended, Plated, Sandwich-Cultured Human Hepatocytes Versus Human Liver Tissue Using Quantitative Targeted Proteomics and Cell Surface Biotinylation [0.03%]
基于定量蛋白质组学和细胞表面生物素标记的人肝组织与悬浮、贴壁及夹心培养人肝细胞转运体总量及质膜丰度的比较分析
Vineet Kumar,Laurent Salphati,Cornelis E C A Hop et al.
Vineet Kumar et al.
Suspended (SH), plated (PH), and sandwich-cultured hepatocytes (SCH) are commonly used models to predict in vivo transporter-mediated hepatic uptake (SH or PH) or biliary (SCH) clearance of drugs. When doing so, the total and the plasma mem...
Effect of Osmolality on the Pharmacokinetic Interaction between Apple Juice and Atenolol in Rats [0.03%]
渗透压对苹果汁与阿替洛尔在大鼠体内动力学相互作用的影响
Yuta Funai,Yoshiyuki Shirasaka,Marika Ishihara et al.
Yuta Funai et al.
A recent clinical study reported that the ingestion of apple juice (AJ) markedly reduced the plasma concentration of atenolol; however, our in vitro study showed that atenolol may not be a substrate of organic anion transporting polypeptide...