Intestine versus liver? Uncovering the hidden major metabolic organs of silybin in rats [0.03%]
肠道还是肝脏？揭秘乳蓟素主要代谢器官及其机制_rat
Yuanbo Sun,Like Xie,Jing Zhang et al.
Yuanbo Sun et al.
Silybin, a milk thistle extract, is a flavonolignan compound with hepatoprotective effect. It is commonly used in dietary supplements, functional foods, and nutraceuticals. However, the metabolism of silybin has not been systematically char...
Xin Chen,Chunying Gao,Lyrialle W Han et al.
Xin Chen et al.
Evidence-based dose selection of drugs in pregnant women has been lacking because of challenges in studying maternal-fetal pharmacokinetics. Hence, many drugs are administered off-label during pregnancy based on data obtained from nonpregna...
Pharmacokinetics and absorption, distribution, metabolism and excretion profiling of tanimilast following an intravenous 14C-microtracer coadministered with an inhaled dose in healthy male individuals [0.03%]
健康男性受试者中，静脉注射微量示踪剂放射性碳-塔西米拉司后的药代动力学及吸收、分布、代谢和排泄研究
Michele Bassi,Veronica Puviani,Debora Santoro et al.
Michele Bassi et al.
Tanimilast is an inhaled phosphodiesterase-4 inhibitor currently in phase III clinical development for treating chronic obstructive pulmonary disease and asthma. This trial aimed to characterize the pharmacokinetics, mass balance, and metab...
Real-world application of physiologically based pharmacokinetic models in drug discovery [0.03%]
生理药动学模型在药物发现中的实际应用
Laura G A Santos,Swati Jaiswal,Kuan-Fu Chen et al.
Laura G A Santos et al.
The utility of physiologically based pharmacokinetic (PBPK) models in support of drug development has been well documented. During the discovery stage, PBPK modeling has increasingly been applied for early risk assessment, prediction of hum...
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%]
人肝样本中构成性雄烷受体(CAR或NR1I3)转录因子的异构体水平表达更好地预测细胞色素P450的mRNA表达
Joseph M Collins,Danxin Wang
Joseph M Collins
Many factors cause interperson variability in the activity and expression of the cytochrome P450 (CYP) drug-metabolizing enzymes in the liver, leading to variable drug exposure and treatment outcomes. Several liver-enriched transcription fa...
Heterotropic allosteric modulation of CYP3A4 in vitro by progesterone: Evidence for improvement in prediction of time-dependent inhibition for macrolides [0.03%]
孕酮对CYP3A4的别构调节作用及其对大环内酯类药物时间依赖性抑制预测的影响
Luc R A Rougée,Pooja V Hegde,Kaitlin Shin et al.
Luc R A Rougée et al.
Predictions of drug-drug interactions resulting from time-dependent inhibition (TDI) of CYP3A4 have consistently overestimated or mispredicted (ie, false positives) the interaction that is observed in vivo. Recent findings demonstrated that...
Environmentally persistent free radicals stimulate CYP2E1-mediated generation of reactive oxygen species at the expense of substrate metabolism [0.03%]
环境持久自由基介导CYP2E1生成活性氧而非底物代谢
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...
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2参与生成5-羧基吡非尼酮（一种吡非尼酮主要代谢产物）的表征研究
Rei Sato,Tatsuki Fukami,Kazuya Shimomura et al.
Rei Sato et al.
Pirfenidone (PIR) is used in the 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),...
Potential and challenges in application of physiologically based pharmacokinetic modeling in predicting diarrheal disease impact on oral drug pharmacokinetics [0.03%]
生理药动学模型在预测腹泻对口服药物药动学影响中的潜力与挑战
Cindy X Zhang,Samuel L M Arnold
Cindy X Zhang
Physiologically based pharmacokinetic (PBPK) modeling is a physiologically relevant approach that integrates drug-specific and system parameters to generate pharmacokinetic predictions for target populations. It has gained immense popularit...
Human enteroid monolayers: A novel, functionally stable model for investigating oral drug disposition [0.03%]
人源肠类器官单层模型：一种新型的功能稳定的肠道吸收模型用于研究药物处置属性
Christopher Arian,Eimear O&#x;Mahony,James W MacDonald et al.
Christopher Arian et al.
To further the development of an in vitro model that faithfully recapitulates drug disposition of orally administered drugs, we investigated the utility of human enteroid monolayers to simultaneously assess intestinal drug absorption and fi...