Uncovering the Impact of COVID-19 Mediated Bidirectional Dysregulation of CYP3A4 on Systemic and Pulmonary Drug Concentrations Using Physiologically Based Pharmacokinetic Modeling [0.03%]
基于生理的药代动力学模型揭示COVID-19介导的CYP3A4双向失调对全身和肺药物浓度的影响
Chukwunonso K Nwabufo
Chukwunonso K Nwabufo
Several clinical studies have shown that COVID-19 increases the systemic concentration of drugs in hospitalized COVID-19 patients. However, it is unclear how COVID-19-mediated bidirectional dysregulation of hepatic and pulmonary CYP3A4 impa...
Heterotropic Allosteric Modulation of CYP3A4 In Vitro by Progesterone: Evidence for Improvement in Prediction of Time Dependent Inhibition for Macrolides [0.03%]
孕酮异otropic别构调节CYP3A4体外：为改善大环内酯类药物时间依赖性抑制预测的证据
Luc R A Rougee,Pooja V Hegde,Kaitlin Shin et al.
Luc R A Rougee et al.
Predictions of drug-drug interactions resulting from time-dependent inhibition (TDI) of CYP3A4 have consistently overestimated or mis-predicted (i.e. false positives) the interaction that is observed in vivo. Recent findings demonstrated th...
Pharmacokinetics and ADME Profiling of Tanimilast Following an Intravenous 14C-Microtracer co-administered with an Inhaled Dose in Healthy Male Individuals [0.03%]
健康男性受试者中静脉注射示踪剂量的塔纳米司特的药代动力学及ADME特征分析
Michele Bassi,Veronica Puviani,Debora Santoro et al.
Michele Bassi et al.
Tanimilast is an inhaled phosphodiesterase-4 inhibitor currently in phase 3 clinical development for treating chronic obstructive pulmonary disease (COPD) and asthma. This trial aimed to characterize the pharmacokinetics, mass balance, and ...
Characterization of human alcohol dehydrogenase 4 and aldehyde dehydrogenase 2 as enzymes involved in the formation of 5-carboxylpirfenidone, a major metabolite of pirfenidone [0.03%]
人类酒精脱氢酶4和醛脱氢酶2参与形成5-羧基吡非尼酮（一种主要的吡非尼酮代谢产物）的表征研究
Rei Sato,Tatsuki Fukami,Kazuya Shimomura et al.
Rei Sato et al.
Pirfenidone (PIR) is used to treatment of idiopathic pulmonary fibrosis. After oral administration, it is metabolized by cytochrome P450 1A2 to 5-hydroxylpirfenidone (5-OH PIR) and further oxidized to 5-carboxylpirfenidone (5-COOH PIR), a m...
Utility of Common In Vitro Systems for Predicting Circulating Metabolites [0.03%]
预测循环代谢物的体外模型的适用性研究
Elyse C Freiberger,Michael P Thompson,Xiaomei Zhang et al.
Elyse C Freiberger et al.
In vitro systems such as cultured hepatocytes are used early in drug development as a proxy for in vivo data to predict metabolites in human and the potential preclinical species. These data support preclinical species selection for toxicit...
Environmentally Persistent Free Radicals stimulate CYP2E1-mediated generation of reactive oxygen species at the expense of substrate metabolism [0.03%]
持久自由基刺激CYP2E1介导的活性氧生成以牺牲底物代谢为代价
George F Cawley,J Patrick Connick,Marilyn K Eyer et al.
George F Cawley et al.
Environmentally persistent free radicals (EPFRs) are a recently recognized component of particulate matter that cause respiratory and cardiovascular toxicity. The mechanism of EPFR toxicity appears to be related to their ability to generate...
Isoform-level expression of the constitutive androstane receptor (CAR or NR1I3) transcription factor better predicts the mRNA expression of the cytochrome P450s in human liver samples [0.03%]
人肝样本中组成型雄烷受体(CAR或NR1I3)转录因子的异构体表达水平更好地预测细胞色素P450的mRNA表达水平
Joseph M Collins,Danxin Wang
Joseph M Collins
Many factors cause inter-person variability in the activity and expression of liver cytochrome P450 (CYP) drug-metabolizing enzymes, leading to variable drug exposure and treatment outcomes. Several liver-enriched transcription factors (TFs...
Absolute Membrane Protein Abundance of P-gp, BCRP and MRPs in Term Human Placenta Tissue and Commonly Used Cell Systems: Application in PBPK Modeling of Placental Drug Disposition [0.03%]
人胎盘组织及常用细胞系统中P-糖蛋白、乳腺癌耐药蛋白和多药耐药蛋白的绝对膜蛋白丰度：在胎盘药物分布生理基底药物动力学建模中的应用
Zubida M Al-Majdoub,Jolien J M Freriksen,Angela Colbers et al.
Zubida M Al-Majdoub et al.
The placenta acts as a barrier, excluding noxious substances whilst actively transferring nutrients to the fetus, mediated by various transporters. This study quantified the expression of key placental transporters in term human placenta (n...
Intestine vs. Liver ？ Uncovering the Hidden major Metabolic organs of Silybin in Rats [0.03%]
肠道VS肝脏？揭秘白杨黄素在大鼠体内的主要代谢器官
Yuanbo Sun,Like Xie,Jing Zhang et al.
Yuanbo Sun et al.
Silybin, extracted milk thistle, was a flavonolignan compound with hepatoprotective effect. Now it is commonly used in dietary supplements, functional foods, and nutraceuticals. However, the metabolism of silybin has not been systematically...
50th Anniversary Celebration Collection Special Section on New and Emerging Areas and Technologies in Drug Metabolism and Disposition, Part II-Editorial [0.03%]
纪念特刊：药物代谢与处置新领域和技术周年庆专题（第二部分）-主编序言
Xiao-Bo Zhong,Yurong Lai,Xinxin Ding
Xiao-Bo Zhong