Abstract:
INTRODUCTION:This meeting report presents a brief summary on the 4th Annual Predictive Toxicology Summit 2012, which was held on 15 - 16 February 2012 in London. AREAS COVERED:The majority of presentations came from global pharmaceutical companies, although small and medium enterprise (SME) and academic researchers were represented too. Major regulatory bodies were also present. The article highlights the summit, which was considered a good learning opportunity to catch up on the recent advances in predictive toxicology. EXPERT OPINION:Predictive toxicology has become more and more important due to social and economic pressure and scientific reasons. Technological developments are rapid, but there is a gulf between the technology developers and the pharmaceutical end users; hence, early engagement is desirable. Stem cell-derived cell-based assays as well as three-dimensional in vitro tissue/organ model development are within the reach now, but a lot needs to be done to optimise and validate the developed protocols and products. The field of predictive toxicology needs fundamental research of interdisciplinary nature, which requires much needed trained personnel and funding.
journal_name
Expert Opin Drug Metab Toxicoljournal_title
Expert opinion on drug metabolism & toxicologyauthors
Cui Zdoi
10.1517/17425255.2013.802306subject
Has Abstractpub_date
2013-08-01 00:00:00pages
1061-6issue
8eissn
1742-5255issn
1744-7607journal_volume
9pub_type
杂志文章abstract:INTRODUCTION:The fixed-dose combination therapy of sofosbuvir (SOF) plus velpatasvir (VEL) is the first pangenotypic, direct-acting antiviral (DAA), single-treatment regimen (STR) for the treatment of hepatitis C virus (HCV) infection to be commercialized. It is approved for the treatment of HCV genotypes 1, 2, 3, 4, 5...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2017.1292253
更新日期:2017-04-01 00:00:00
abstract:INTRODUCTION:The fixed-dose combination of three direct-acting antivirals (DAA), namely sofosbuvir, velpatasvir and voxilaprevir is the first pangenotypic, single tablet regimen developed for the treatment of HCV infection. Areas covered: The pharmacokinetics, pharmacodynamics, efficacy and safety of the co-formulation...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2017.1359254
更新日期:2017-09-01 00:00:00
abstract:INTRODUCTION:Multiple myeloma (MM) patients who relapse, or become refractory to currently available novel agents, have limited treatment options with poor outcomes. The introductions of the newer proteasome inhibitor carfilzomib and the immunomodulatory agent pomalidomide have provided new treatment strategies within ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2013.827169
更新日期:2013-11-01 00:00:00
abstract:INTRODUCTION:Drug ototoxicity represents one of the main preventable causes of deafness. Ototoxicity is a trait shared by aminoglycoside and macrolide antibiotics, antimalarial medications, loop diuretics, platinum-based chemotherapeutic agents, some NSAIDs and most recently described, acetaminophen when abused with na...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.614231
更新日期:2011-12-01 00:00:00
abstract::Several first-line antihypertensive drugs, including calcium channel blockers, beta-adrenergic blockers and angiotensin receptor blockers, undergo metabolism through different CYP isoforms. As a consequence of CYP-dependent metabolism, wide interindividual variability of plasma concentrations of antihypertensive drugs...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425250903397381
更新日期:2010-02-01 00:00:00
abstract:INTRODUCTION:The absorption, distribution, metabolism, excretion and toxicity (ADME-tox) processes of drugs are of importance and require preclinical investigation intestine in addition to the liver. Various models have been developed for prediction of ADME-tox in the intestine. In this review, precision-cut intestinal...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2016.1125882
更新日期:2016-01-01 00:00:00
abstract::The human ether-a-go-go-related gene (hERG) encodes the pore-forming alpha-subunit of a voltage-gated potassium (K(+)) channel. A variety of unrelated compounds reduce K(+ )current in the heart by blocking the pore or disrupting trafficking of the hERG channel to the membrane surface. This induces a syndrome known as ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2.1.81
更新日期:2006-02-01 00:00:00
abstract:INTRODUCTION:A major challenge in transplantation is improving long-term organ transplant and patient survival. Immunosuppressants protect the transplant organ from alloimmune reactions, but sometimes also exhibit limiting side effects. The key to improving long-term outcome following transplantation is the selection o...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.544249
更新日期:2011-02-01 00:00:00
abstract:INTRODUCTION:Cytochromes P450 (P450) and associated monooxygenases are a family of heme proteins involved in metabolism of endogenous compounds (arachidonic acid, eicosanoids and prostaglandins) as also xenobiotics including drugs and environmental chemicals. Liver is the major organ involved in P450-mediated metabolis...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2013.759208
更新日期:2013-05-01 00:00:00
abstract::Rats are an important tool in pharmacology and toxicology. The authors focus on rat P450s in relation to diazepam metabolism. In particular, considerable attention is devoted to the CYP2D subfamily, which is a group of highly polymorphic enzymes. First, the metabolic profiles of diazepam of humans and other animals ar...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425250903207002
更新日期:2009-11-01 00:00:00
abstract::The pharmaceutical relevance of proton-coupled peptide transporters is currently under intense investigation in many laboratories. Studies have shown that these membrane proteins, expressed in intestine, kidney, choroid plexus and other tissues, accept many peptidomimetic drugs and prodrugs as substrates. The focus of...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425250903042292
更新日期:2009-08-01 00:00:00
abstract::Elevated serum cholesterol is a known risk factor for the development of coronary artery disease. Circulating cholesterol is a product of both cholesterol absorption from the gut and cellular cholesterol production. Ezetimibe is a novel cholesterol-lowering drug that acts at the brush border of the small intestine. Re...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.3.3.441
更新日期:2007-06-01 00:00:00
abstract:INTRODUCTION:Emtricitabine/tenofovir disoproxil fumarate fixed-dose combination (FTC/TDF FDC) is the co-formulation of a nucleoside and a nucleotide, respectively. After oral administration, both drugs exhibit plasma and intracellular half-lives suitable for once-daily dosing. Within the host cells, active metabolites ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2012.714367
更新日期:2012-10-01 00:00:00
abstract::There is wide inter-individual variability in the pharmacokinetics, pharmacodynamics and tolerance of anticancer drugs. Recent evidence suggests that there is even greater variability between individuals of different ethnicity. Allelic variants of genes encoding drug metabolising enzymes are expressed with different i...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425250902800153
更新日期:2009-03-01 00:00:00
abstract:INTRODUCTION:The second-line treatment of endometriosis-related pain symptoms includes injectable depot formulations of gonadotropin-releasing hormone analogs (GnRH-as). These drugs improve the symptomatology by inducing a hypoestrogenic status and a consequent regression of endometriotic implants. However, GnRH-a may ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章
doi:10.1080/17425255.2020.1789591
更新日期:2020-09-01 00:00:00
abstract::Introduction: The treatment of psoriasis with conventional topical therapies and disease-modifying anti-rheumatic drugs (DMARDs) is often linked to unsatisfactory outcomes and the risk of serious adverse events. Over the last decades, research advances in understanding the role of tumor necrosis factor alpha (TNF α) a...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2019.1681969
更新日期:2019-11-01 00:00:00
abstract::Introduction: The inclusion of pharmacogenetics alongside clinical information in anticoagulant therapy offers the opportunity for a tailored approach to treatment according to individual patient characteristics. Areas covered: Literature was searched using PubMed database, focusing on pharmacogenetics of oral anticoa...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2019.1623878
更新日期:2019-06-01 00:00:00
abstract:INTRODUCTION:Whereas in the past, (Q)SAR methods have been largely used to support the design of new drugs, in the last few decades, there has been a new interest in its applications for the assessment of drug safety. In particular, the ICH M7 guideline has introduced the concept that (Q)SAR predictions for the Ames mu...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章
doi:10.1080/17425255.2020.1785428
更新日期:2020-08-01 00:00:00
abstract:INTRODUCTION:The association between pregnancy and altered drug pharmacokinetic (PK) properties is acknowledged, as is its impact on drug plasma concentrations and thus therapeutic efficacy. However, there have been few robust PK studies of antimalarial use in pregnancy. Given that inadequate dosing for prevention or t...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章
doi:10.1080/17425255.2020.1802425
更新日期:2020-09-01 00:00:00
abstract:INTRODUCTION:Medication of pregnant women is increasingly common in developed countries. Several placental drug transporters have been shown to transfer their substrates from the trophoblast back to the maternal circulation, thus hindering the transplacental passage of xenobiotics and protecting the fetus. However, the...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.1005073
更新日期:2015-04-01 00:00:00
abstract::Antithrombotic therapies form the cornerstone of management of acute coronary syndromes (ACS). An ideal antithrombotic agent should reduce ischemic complications while keeping bleeding events to a minimum. Heparins, both unfractionated and low molecular weight, reduce ischemic outcomes but also significantly increase ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425250903456039
更新日期:2009-12-01 00:00:00
abstract:INTRODUCTION:Catechins of green tea extract (GTE) have been associated with the rare risk of hepatotoxicity in a few individuals. As GTE were coadministered with synthetic drugs in some hepatotoxicity cases, uncertainty emerged whether GTE are a risk factor of drug-induced liver injury (DILI). AREAS COVERED:Case repor...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2014.971011
更新日期:2014-12-01 00:00:00
abstract:BACKGROUND:Obesity, hypertension and Type 2 diabetes are major contributing factors to the increase in the number of patients that have chronic kidney disease. The clustering of visceral obesity and cardiovascular risk factors has been designated metabolic syndrome or cardiometabolic syndrome. Cardiometabolic syndrome ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.4.2.165
更新日期:2008-02-01 00:00:00
abstract::Pathologists play a central role in the recognition and prevention of drug-induced toxicity. Pathologists engaged in clinical practice must identify a pattern of histological lesions that are interpreted in concert with a variety of clinical data to determine the probability of drug-induced toxicity versus background ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2.2.241
更新日期:2006-04-01 00:00:00
abstract:BACKGROUND:A growing body of evidence suggests that everolimus might offer effective immunosuppressive activity together with antiproliferative effects that may address some of the unmet needs in the long-term therapeutic management of the post-transplant patient. OBJECTIVE:To summarize the emerging evidence for emplo...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.4.6.807
更新日期:2008-06-01 00:00:00
abstract:INTRODUCTION:It is widely accepted that current practice of polypharmacy inevitably increases the incidence of drug-drug interactions (DDIs). Serious DDIs are a major liability for new molecular entities entering the pharmaceutical market. Various strategies are employed to avoid problematic compounds for clinical deve...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.1013095
更新日期:2015-04-01 00:00:00
abstract:INTRODUCTION:Chemoprevention of cancer refers to the use of natural or synthetic compounds to abolish or perturb a variety of steps in tumor initiation, promotion, and progression. This can be realized through different mechanisms, including activation of free radical scavenging enzymes, control of chronic inflammation...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章
doi:10.1080/17425255.2021.1839412
更新日期:2021-01-01 00:00:00
abstract:INTRODUCTION:Medullary thyroid carcinoma (MTC) is a rare endocrine malignancy accounting for a significant percentage of thyroid cancer-related fatal events. Traditional treatment modalities used in the other types of thyroid carcinomas have been proved largely ineffective in advanced MTC. Better understanding of the m...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2014.885015
更新日期:2014-03-01 00:00:00
abstract::Acetaminophen (APAP) hepatotoxicity is currently the single most important cause of acute liver failure in the US, and is associated with a significant number of deaths. The toxic response to APAP is triggered by a highly reactive metabolite N-acetyl-p-benzoquinone-imine. Following the hepatocellular initiation events...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2.4.493
更新日期:2006-08-01 00:00:00
abstract:INTRODUCTION:Mathematical models of dermal transport offer the advantages of being much faster and less expensive than in vitro or in vivo studies. The number of methods used to create such models has been increasing rapidly, probably due to the steady rise in computational power. Although each of the various approache...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.1063615
更新日期:2015-01-01 00:00:00