Improved clearance predictions for aldehyde oxidase substrates using a novel triculture human hepatocyte model [0.03%]
使用新型三培养人肝细胞模型改善醛氧化酶底物的清除率预测
Alexander Byer-Alcorace,Cody Thomas,Mitchell E Taub et al.
Alexander Byer-Alcorace et al.
Over the last several decades, efforts in medicinal chemistry have aimed to reduce the extent of CYP metabolism of new chemical entities. This approach, however, has led to increased susceptibility to metabolism by non-CYP-mediated pathways...
Quantitative clinical risk assessment of CYP2C, UDP-glucuronosyltransferase, P-glycoprotein induction, and complex drug-drug interactions using TruVivo human hepatocyte triculture platform [0.03%]
使用TruVivo人肝细胞三化平台对CYP2C，UDP-葡萄糖醛酸转移酶，P-糖蛋白诱导和复杂药物相互作用进行定量临床风险评估
Diane Ramsden,Cody L Fullenwider,Cipriano Santos et al.
Diane Ramsden et al.
Quantitative prediction and clinical risk assessment for induction of drug-metabolizing enzymes and transporters beyond CYP3A has been hindered by low dynamic response in the gold standard hepatocyte monoculture model. A gap in translation ...
Impact of the loss of slc43a3 on 6-mercaptopurine absorption and tissue distribution in mice [0.03%]
slc43a3基因丢失对小鼠6-巯基嘌呤吸收及组织分布的影响
Aaron L Sayler,Hannah Dean,James R Hammond
Aaron L Sayler
6-Mercaptopurine (6-MP) is a nucleobase analog used in the therapy of acute lymphoblastic leukemia and inflammatory bowel disease. It is associated with numerous side effects including myelotoxicity, hepatotoxicity, and gastrointestinal com...
Toward improved clearance predictions and distribution profiles employing the isolated perfused rat liver model: Experimental optimization [0.03%]
利用孤立灌注大鼠肝脏模型提高清除率预测和分布特征描述的实验优化研究
Sofie Heylen,Johan Nicolaï,Stijn Van Asten et al.
Sofie Heylen et al.
To reduce the drug attrition due to failure in clinical trials, an early accurate hepatic clearance (CLH) prediction for small molecule drugs is critical. However, the routinely used in vitro to in vivo extrapolation (IVIVE) methods to pred...
Species-specific in vivo exposure assessment and in vivo-in vitro correlation of the carboxylate esters prodrug HD56 targeting FK506 binding proteins: The pivotal role of humanized mice [0.03%]
针对FK506结合蛋白的目标药物HD56的特异性体内暴露评估及体内体外相关性：人源化小鼠的关键作用
Mengmeng Yang,Shi Yao,Wenpeng Zhang et al.
Mengmeng Yang et al.
HD561, which was designed to enhance nerve growth, was re-engineered into HD56, a carboxylic acid ester prodrug. The goal of this study was to compare the druggability, species differences, and the correlation between in vitro and in vivo t...
Efficient protein quantification in drug metabolism and pharmacokinetics with an accelerated proteomic workflow [0.03%]
在药物代谢和药代动力学中利用加速蛋白质组工作流程有效量化蛋白
Xiaofeng Wu,Nicholas Ferguson,Lloyd Wei Tat Tang
Xiaofeng Wu
Quantifying proteins involved in the absorption, distribution, metabolism, and excretion (ADME) of drugs is essential to improve understanding of their disposition and pharmacokinetics. Proteomics, because of its great versatility, is a wid...
Alterations of valsartan pharmacokinetics in a rodent model of metabolic dysfunction-associated steatohepatitis [0.03%]
代谢功能障碍相关性肝脂肪变大鼠模型中缬沙坦药代动力学的改变
Dominique O Farrera,Mina M Alaaldin,Paige Lindberg et al.
Dominique O Farrera et al.
Valsartan (VAL) is commonly prescribed for patients with cardiovascular disease (CVD) to lower blood pressure, reduce heart failure risk, and prevent heart attacks or strokes by blocking the effects of angiotensin II. Many patients with CVD...
Quantitative prediction of drug disposition for uridine diphosphate-glucuronosyltransferase substrates using humanized mice [0.03%]
使用人源化小鼠对尿苷二磷酸葡萄糖醛酸基转移酶底物的药物处置进行定量预测
Taiji Miyake,Yuito Fujita,Manabu Hirabayashi et al.
Taiji Miyake et al.
Drug clearance and drug-drug interactions are essential for pharmacokinetic assessment. However, current in vitro systems and animal scale-up approaches often fail to accurately predict drug disposition mediated by metabolizing enzymes, esp...
A review of physiologically based pharmacokinetic modeling of renal drug disposition [0.03%]
生理药动学模型在药物肾处置中的应用进展
Weize Huang,Christine Bowman,Mengyue Yin et al.
Weize Huang et al.
The human kidney is a critical organ for the elimination of numerous drugs and metabolites. The mechanisms of renal drug handling are manifold including unbound filtration, transporter-mediated active secretion, bidirectional passive diffus...
Cross-industry demonstration of the validity of the mixed matrix method for the assessment of cross-species exposure coverage of human circulating drug metabolites [0.03%]
混合矩阵方法在评估人类循环药物代谢物的跨物种暴露覆盖率中的有效性跨行业演示
Alexander D James,Christian Lanshoeft,Gregory S Steeno et al.
Alexander D James et al.
The mixed matrix method (MmM) is a widely used approach by the pharmaceutical industry for early assessment of whether exposures to major human circulating metabolites, of traditional small-molecule drugs, are adequately covered by the spec...