The Experts below are selected from a list of 94401 Experts worldwide ranked by ideXlab platform
Wen Xie - One of the best experts on this subject based on the ideXlab platform.
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long noncoding rnas lncrnas in Drug Metabolism and disposition implications in cancer chemo resistance
Acta Pharmaceutica Sinica B, 2020Co-Authors: Yue Wang, Zihui Fang, Mei Hong, Da Yang, Wen XieAbstract:Drug Metabolism is an orchestrated process in which Drugs are metabolized and disposed through a series of specialized enzymes and transporters. Alterations in the expression and/or activity of these enzymes and transporters can affect the bioavailability (pharmacokinetics, or PK) and therapeutic efficacy (pharmacodynamics, or PD) of Drugs. Recent studies have suggested that the long non-coding RNAs (lncRNAs) are highly relevant to Drug Metabolism and Drug resistance, including chemo-resistance in cancers, through the regulation of Drug Metabolism and disposition related genes. This review summarizes the regulation of enzymes, transporters, or regulatory proteins involved in Drug Metabolism by lncRNAs, with a particular emphasis on Drug Metabolism and chemo-resistance in cancer patients. The perspective strategies to integrate multi-dimensional pharmacogenomics data for future in-depth analysis of Drug Metabolism related lncRNAs are also proposed. Understanding the role of lncRNAs in Drug Metabolism will not only facilitate the identification of novel regulatory mechanisms, but also enable the discovery of lncRNA-based biomarkers and Drug targets to personalize and improve the therapeutic outcome of patients, including cancer patients.
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pregnane x receptor and constitutive androstane receptor at the crossroads of Drug Metabolism and energy Metabolism
Drug Metabolism and Disposition, 2010Co-Authors: Jie Gao, Wen XieAbstract:The pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are two closely related and liver-enriched nuclear hormone receptors originally defined as xenobiotic receptors. PXR and CAR regulate the transcription of Drug-metabolizing enzymes and transporters, which are essential in protecting our bodies from the accumulation of harmful chemicals. An increasing body of evidence suggests that PXR and CAR also have an endobiotic function that impacts energy homeostasis through the regulation of glucose and lipids Metabolism. Of note and in contrast, disruptions of energy homeostasis, such as those observed in obesity and diabetes, also have a major impact on Drug Metabolism. This review will focus on recent progress in our understanding of the integral role of PXR and CAR in Drug Metabolism and energy homeostasis.
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animal models of xenobiotic receptors in Drug Metabolism and diseases
Methods in Enzymology, 2005Co-Authors: Haibiao Gong, Michael Sinz, Yan Feng, Taosheng Chen, Raman Venkataramanan, Wen XieAbstract:Drug-metabolizing enzymes, including phase II conjugating enzymes, play an important role in both Drug Metabolism and human diseases. The genes that encode these enzymes and transporters are inducible by numerous xenobiotics and endobiotics and the inducibility shows clear species specificity. In the past several years, orphan nuclear receptors, such as PXR and CAR, have been established as species-specific "xenobiotic receptors" that regulate the expression of phase I and phase II enzymes and Drug transporters. The creation of xenobiotic receptor transgenic and knockout mice has not only provided an opportunity to dissect the transcriptional control of Drug metabolizing enzymes, but also offered a unique opportunity to study the xenobiotic receptor-mediated enzyme regulation in both Drug Metabolism and diseases. "Humanized" hPXR transgenic mice represent a major step forward in the creation and utilization of humanized rodent models for toxicological assessment that may aid in the development of safer Drugs.
Jeffrey C Stevens - One of the best experts on this subject based on the ideXlab platform.
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the human hepatic cytochromes p450 involved in Drug Metabolism
Critical Reviews in Toxicology, 1992Co-Authors: Steven A Wrighton, Jeffrey C StevensAbstract:The cytochromes P450 are a superfamily of hemoproteins that catalyze the Metabolism of a large number of xenobiotics and endobiotics. The type and amount (i.e., the animal's phenotype) of the P450s expressed by the animal, primarily in the liver, thus determine the metabolic response of the animal to a chemical challenge. A majority of the characterized P450s involved in hepatic Drug Metabolism have been identified in experimental animals. However, recently at least 12 human Drug-metabolizing P450s have been characterized at the molecular and/or enzyme level. The characterization of these P450s has made it possible to "phenotype" microsomal samples with respect to their relative levels of the various P450s and their metabolic capabilities. The purpose of this review is to compare and contrast the human P450s involved in Drug Metabolism with their related forms in the rat and other experimental species.
Pavel Anzenbacher - One of the best experts on this subject based on the ideXlab platform.
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cytochromes p450 and experimental models of Drug Metabolism
Journal of Cellular and Molecular Medicine, 2002Co-Authors: Roman Zuber, Eva Anzenbacherova, Pavel AnzenbacherAbstract:For the development of new Drugs, evaluation of Drug-Drug interactions with already known compounds, as well as for better understanding of Metabolism pathways of various toxicants and pollutants, we studied the Drug Metabolism mediated by cytochromes P450. The experimental approach is based on animal Drug-metabolising systems. From the ethical as well as rational reasons, the selection of an appropriate system is crucial. Here, it is necessary to decide on the basis of expected CYP system involved. For CYP1A-mediated pathways, all the commonly used experimental models are appropriate except probably the dog. On the contrary, the dog seems to be suitable for modelling of processes depending on the CYP2D. With CYP2C, which is possibly the most large and complicated subfamily, the systems based on monkey (Maccacus rhesus) may be a good representative. The CYP3A seems to be well modelled by pig or minipig CYP3A29. Detailed studies on activities with individual isolated CYP forms are needed to understand in full all aspects of inter-species differences and variations.
Laura M Shireman - One of the best experts on this subject based on the ideXlab platform.
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interindividual variability in cytochrome p450 mediated Drug Metabolism
Drug Metabolism and Disposition, 2016Co-Authors: Timothy S Tracy, Kenneth E. Thummel, Hyunyoung Jeong, Bhagwat Prasad, Amarjit S Chaudhry, Erin G Schuetz, Xiaobo Zhong, Yun Chen Tien, Xian Pan, Laura M ShiremanAbstract:The cytochrome P450 (P450) enzymes are the predominant enzyme system involved in human Drug Metabolism. Alterations in the expression and/or activity of these enzymes result in changes in pharmacokinetics (and consequently the pharmacodynamics) of Drugs that are metabolized by this set of enzymes. Apart from changes in activity as a result of Drug-Drug interactions (by P450 induction or inhibition), the P450 enzymes can exhibit substantial interindividual variation in basal expression and/or activity, leading to differences in the rates of Drug elimination and response. This interindividual variation can result from a myriad of factors, including genetic variation in the promoter or coding regions, variation in transcriptional regulators, alterations in microRNA that affect P450 expression, and ontogenic changes due to exposure to xenobiotics during the developmental and early postnatal periods. Other than administering a probe Drug or cocktail of Drugs to obtain the phenotype or conducting a genetic analysis to determine genotype, methods to determine interindividual variation are limited. Phenotyping via a probe Drug requires exposure to a xenobiotic, and genotyping is not always well correlated with phenotype, making both methodologies less than ideal. This article describes recent work evaluating the effect of some of these factors on interindividual variation in human P450-mediated Metabolism and the potential utility of endogenous probe compounds to assess rates of Drug Metabolism among individuals.
Joseph A Carcillo - One of the best experts on this subject based on the ideXlab platform.
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cytochrome p450 mediated Drug Metabolism is reduced in children with sepsis induced multiple organ failure
Intensive Care Medicine, 2003Co-Authors: Joseph A Carcillo, Lesley Doughty, Danny Kofos, Reginald F Frye, Sandra S Kaplan, Howell Sasser, Gilbert J BurckartAbstract:Objective Antipyrine Metabolism is a "gold standard" measure of mixed cytochrome P450 (CYP) mediated Drug Metabolism in humans. Cytokines (e.g., interleukin-6) and nitric oxide reduce CYP 450 activity in vitro and in vivo. Because interleukin-6 and nitric oxide production increases in children with sepsis-induced multiple organ failure, we hypothesized impaired CYP 450 mediated Drug Metabolism in this population.
