Abstract:
INTRODUCTION:If a drug is found to be an inducer of hepatic drug metabolizing enzymes via activation of nuclear receptors such as pregnane X receptor (PXR) or constitutive androstane receptor (CAR), it is likely that drug transporters regulated through these same receptors will be induced as well. This review highlights what is currently known about the molecular mechanisms that regulate transporter expression and where the research is directed. Areas covered: This review is focused on publications that describe the role of activated hepatic nuclear receptors in the subsequent regulation of drug uptake and/or efflux transporters following exposure to xenobiotics. Expert opinion: Many of the published studies on the role of nuclear receptors in the regulation of drug transporters involve non-human test animals. But due to species response differences, these associations are not always applicable to humans. For this reason, some relevant human in vitro models have been developed, such as primary or cryopreserved human hepatocytes, human liver slices, or HepG2 or HuH7 cell lines transiently or stably transfected with PXR expression and reporter constructs as well as in vivo models such as PXR-humanized mice. These human-relevant test systems will continue to be developed and applied for the testing of investigational drugs.
journal_name
Expert Opin Drug Metab Toxicoljournal_title
Expert opinion on drug metabolism & toxicologyauthors
Amacher DEdoi
10.1080/17425255.2016.1223626subject
Has Abstractpub_date
2016-12-01 00:00:00pages
1463-1477issue
12eissn
1742-5255issn
1744-7607journal_volume
12pub_type
杂志文章,评审abstract::Luminogenic cytochrome P450 (CYP) assays couple CYP enzyme activity to firefly luciferase luminescence in a technology called P450-Glo(TM) (Promega). Luminogenic substrates are used in assays of human CYP1A1, -1A2, -1B1, -2C8, -2C9, -2C19, -2D6, -2J2, -3A4, -3A7, -4A11, -4F3B, -4F12 and -19. The assays detect dose-dep...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2.4.629
更新日期:2006-08-01 00:00:00
abstract:INTRODUCTION:Apigenin, a natural flavone, is widely distributed in plants such as celery, parsley and chamomile. It is present principally as glycosylated in nature. Higher intake of apigenin could reduce the risk of chronic diseases. It has gained particular interest in recent years as a beneficial, health-promoting a...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2017.1251903
更新日期:2017-03-01 00:00:00
abstract:INTRODUCTION:In vitro genotoxicity assays have a high sensitivity to detect rodent carcinogens, but mammalian cell tests have a propensity for misleading positive results (poor specificity). Recent data show a greater risk of misleading positive results in p53-deficient rodent cell lines than in p53-competent human cel...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.627855
更新日期:2011-12-01 00:00:00
abstract::Pharmacogenetics is the study of the role of genetics in inter-individual variability to drug response and therapy. This review provides a comprehensive report of the present status of pharmacogenetic studies for opioid drugs. Opioid analgesics are widely used clinically for pain management, and inter-patient variabil...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.4.1.77
更新日期:2008-01-01 00:00:00
abstract:INTRODUCTION:Coumadin (R/S-warfarin) is the most widely prescribed oral anticoagulant in the world; nevertheless, its clinical use is complicated by unpredictability in dose requirements to achieve and maintain optimal anticoagulation. Variations in warfarin metabolism among patients contribute to unpredictability in t...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.576247
更新日期:2011-07-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:The prevalence of acute renal allograft rejection has decreased substantially in past decades due to new and more specific immunosuppressive compounds but improvements in long-term graft function have not been achieved. There is a large need for new immunosuppressive agents that lack toxicity of...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.540238
更新日期:2011-01-01 00:00:00
abstract:INTRODUCTION:Variations in the human genome sequence sometimes play an important role in pharmacokinetics and/or pharmacodynamics. Previous studies have demonstrated a high degree of variation both between and within different ethnic populations. Areas covered: This review sought to summarize key SNPs in CYP2B6, CYP3A ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2017.1391214
更新日期:2017-11-01 00:00:00
abstract:INTRODUCTION:Short- and long-acting β agonists (SABA and LABA) are bronchodilators for treating asthma. Bronchodilator response (BDR) is quantified by measuring air expired in the first second during a forced expiratory maneuver, prior to and following inhalation of SABA. BDR has been associated with a significant degr...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2014.939956
更新日期:2014-09-01 00:00:00
abstract:INTRODUCTION:Epigenetics is a rapidly growing field describing heritable alterations in gene expression that do not involve DNA sequence variations. Advances in epigenetics and epigenomics have influenced pharmacology, leading to the development of a new specialty, pharmacoepigenetics, the study of the epigenetic basis...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2017.1260546
更新日期:2017-04-01 00:00:00
abstract:OBJECTIVE:To investigate the metabolic routes and metabolites of myricitrin, an important active ingredient of traditional herbal medicine, yielded by the isolated human intestinal bacteria, which have not been reported previously. METHODS:Fresh human fecal samples were collected from a healthy female volunteer and ab...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章
doi:10.1517/17425255.2014.918954
更新日期:2014-07-01 00:00:00
abstract:INTRODUCTION:Obesity is an epidemic associated with significant morbidity. Lorcaserin , a novel serotonin 2C receptor antagonist, was recently approved as an adjunct to lifestyle modification for long-term weight loss and maintenance. Clinical studies in patients without diabetes demonstrated 5.8% mean weight loss from...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2013.798643
更新日期:2013-08-01 00:00:00
abstract:INTRODUCTION:Topotecan was initially approved for the treatment of recurrent ovarian cancer. In cervical cancer, it has been investigated for its potential as part of systemic therapy for advanced and/or recurrent disease and in combination with cisplatin and radiation as a first-line treatment for advanced disease. As...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2013.758249
更新日期:2013-02-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:Iloperidone is a newly commercialized second-generation (atypical) antipsychotic approved for the acute treatment of schizophrenia in adults. AREAS COVERED IN THIS REVIEW:the purpose of this review is to describe the pharmacokinetic profile of iloperidone and its clinical implications in the tr...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2010.531259
更新日期:2010-12-01 00:00:00
abstract:INTRODUCTION:The elucidation of the toxicological mechanisms of herbal medicines is becoming more and more important with the increasing application of herbal medicines, for treatment of various diseases and the promotion of health. Furthermore, it is widely recognized that as herbal components undergo bioactivation, t...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.586335
更新日期:2011-08-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:Cytochrome (CYP) P450 is a collective name for a very large group of heme enzymes, which catalyze largely oxidative reactions, including those of pharmacological and toxicological importance. Their efficient operation requires coupling of specific electron donor and O(2) consumption and substrat...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425250903329095
更新日期:2010-01-01 00:00:00
abstract::Background: The liver plays a central role in human drug metabolism. To model drug metabolism, the major cell type of the liver, the hepatocyte, is commonly used. Hepatocytes can be derived from human and animal sources, including pluripotent stem cells. Cell-based models have shown promise in modeling human drug expo...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章
doi:10.1080/17425255.2019.1558208
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:5-Aminosalicylate (5-ASA) agents are the mainstay of oral therapy for ulcerative colitis (UC). Balsalazide, a prodrug of 5-ASA, has recently been approved for the treatment of UC. OBJECTIVE:To summarize current data on balsalazide and to discuss its impact on management of UC. METHODS:A systematic review o...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425250903206996
更新日期:2009-10-01 00:00:00
abstract:INTRODUCTION:First- and second-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, erlotinib, icotinib, and afatinib are the standard-of-care for first-line therapy of non-small-cell lung cancer (NSCLC) harboring activating EGFR mutations. Unfortunately, after initial ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2017.1401064
更新日期:2017-12-01 00:00:00
abstract:INTRODUCTION:Iron overload is an inevitable consequence of transfusion therapy for a variety of underlying anemias. Iron overload, without effective chelation, will lead to significant morbidity and mortality. Deferasirox (Exjade®) is an oral tridentate iron chelator used for reducing iron overload. AREAS COVERED:In a...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2012.640674
更新日期:2012-01-01 00:00:00
abstract:INTRODUCTION:Gut microbiota plays critical roles in drug metabolism. The variation of gut microbiota contributes to the interindividual differences toward drug therapy including drug-induced toxicity and efficacy. Accordingly, the investigation and elucidation of gut microbial impacts on drug metabolism and toxicity wi...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2016.1121234
更新日期:2016-01-01 00:00:00
abstract:INTRODUCTION:Drug metabolism is one of the most important processes involving a drug after administration. Undesirable pharmacokinetic properties may lead to drug discontinuation. In the past several decades, a number of drugs have been withdrawn from the market due to safety issues caused by metabolites, especially re...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2018.1519546
更新日期:2018-10-01 00:00:00
abstract:INTRODUCTION:Approaches aiming to model the time course of tumor growth and tumor growth inhibition following a therapeutic intervention have recently been proposed for supporting decision making in oncology drug development. When considered in a comprehensive model-based approach, tumor growth can be included in the c...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2012.693480
更新日期:2012-09-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:many promising targeted agents and combination therapies are being investigated for brain cancer. However, the results from recent clinical trials have been disappointing. A better understanding of the disposition of drug in the brain early in drug development would facilitate appropriate channe...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2010.523420
更新日期:2010-12-01 00:00:00
abstract::It has increasingly been recognized that few molecules move across the cell membrane without the assistance of transporter proteins. Large superfamilies of transporter proteins have been identified in every living cell, including microorganisms and mitochondria. This report reviews the role of transporters in physiolo...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425250903176421
更新日期:2009-11-01 00:00:00
abstract:INTRODUCTION:Adverse drug reactions with an immune pathogenesis are a problem in the clinic and an impediment to drug development. T lymphocytes are believed to play a role in the pathogenesis; however, the nature of the drug interaction with immune receptors remains an area of debate. AREAS COVERED:This article revie...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.992780
更新日期:2015-03-01 00:00:00
abstract:OBJECTIVES:A medical need remains for a once-daily insulin with 24-h basal coverage in all patients. We characterize the steady-state (SS) pharmacokinetic/pharmacodynamic properties of insulin degludec (IDeg) versus insulin glargine (IGlar). RESEARCH DESIGN AND METHODS:In this controlled, single-center study, 66 type ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,随机对照试验
doi:10.1517/17425255.2015.1058779
更新日期:2015-01-01 00:00:00
abstract::Changes in mammalian diets alter the hepatic expression of CYP drug-metabolising enzymes and endobiotic oxidases. Thus, dietary constituents may significantly influence the duration of action of chemicals in tissues. Recent improvements in the mechanistic information on the regulation of constitutive and inducible exp...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.3.2.185
更新日期:2007-04-01 00:00:00
abstract:INTRODUCTION:Therapeutic hypothermia is being employed clinically due to its neuro-protective benefits. Both critical illness and therapeutic hypothermia significantly affect drug disposition, potentially contributing to drug-therapy and drug-disease interactions. Currently, there is limited information on the known al...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.574127
更新日期:2011-07-01 00:00:00
abstract:INTRODUCTION:Cervical cancer is the second-most common malignancy in women worldwide. Cisplatin was introduced as a radiosensitizer in 1999 to improve chances of survival. Tumor cell hypoxia, however, remains a major limiting factor in the treatment of solid tumors with chemotherapy and radiation. There has since been ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2012.730518
更新日期:2012-12-01 00:00:00
abstract::The burden of seasonal influenza in children is poorly recognized, in spite of the potential for severe and even life-threatening illness and common secondary complications. Children are a primary reservoir for the spread of influenza to both family members and the community, which imposes a sizeable social and econom...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.3.5.755
更新日期:2007-10-01 00:00:00