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 of the correct immunosuppressive regimen for an individual patient for minimizing toxicity while maintaining immunosuppressive efficacy. AREAS COVERED:Proteomics and metabolomics have the potential to develop sensitive and specific diagnostic tools for monitoring early changes in cell signal transduction, regulation and biochemical pathways. Here, we review the steps required for the development of molecular markers from discovery, mechanistic and clinical qualification to regulatory approval, and present a critical discussion of the current status of molecular marker development as relevant for the management and individualization of immunosuppressive drug regimens. EXPERT OPINION:Although metabolomics and proteomics-based studies have yielded several candidate molecular markers, most published studies are poorly designed, statistically underpowered and/or often have not gone beyond the discovery stage. Most molecular marker candidates are still at an early stage. Due to the high complexity of and the resources required for diagnostic marker development, initiatives and consortia organized and supported by funding agencies and regulatory agencies will be critical.
journal_name
Expert Opin Drug Metab Toxicoljournal_title
Expert opinion on drug metabolism & toxicologyauthors
Christians U,Klawitter J,Klawitter J,Brunner N,Schmitz Vdoi
10.1517/17425255.2011.544249subject
Has Abstractpub_date
2011-02-01 00:00:00pages
175-200issue
2eissn
1742-5255issn
1744-7607journal_volume
7pub_type
杂志文章,评审abstract:INTRODUCTION:A more concentrated insulin glargine formulation, containing 300 U/mL (Gla-300) was approved in 2015 in the US and Europe for the treatment of diabetes mellitus in adults. AREAS COVERED:This drug evaluation focuses on the pharmacokinetics (PK) and pharmacodynamics (PD) of Gla-300 from studies published up...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2016.1202916
更新日期:2016-08-01 00:00:00
abstract::With the progressive ageing of the population, an increasing number of elderly patients are being exposed to multiple drugs because of co-existing morbidity states requiring pharmacological management. However, the knowledge of the effects of ageing on the pharmacokinetics and pharmacodynamics of individual drugs is f...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 社论,评审
doi:10.1517/17425255.3.3.315
更新日期:2007-06-01 00:00:00
abstract:INTRODUCTION:. Membrane transporters are integral to the maintenance of cellular integrity of all tissue and cell types. While transporters play an established role in the systemic pharmacokinetics of therapeutic drugs, tissue specific expression of uptake transporters can serve as an initiating mechanism that governs ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2020.1755253
更新日期:2020-06-01 00:00:00
abstract:INTRODUCTION:Various trials have attempted to develop gene expression profiles (GEPs) that may provide a better predictor of clinical outcome over traditional clinicopathological criteria. AREAS COVERED:The review focuses on two main areas: trials examining chemotherapy-induced GEP changes pre- and post-treatment, and...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2012.694867
更新日期:2012-09-01 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::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:BACKGROUND:CYP enzymes from the CYP2C and CYP2J subfamilies metabolize arachidonic acid in a regiospecific and stereoselective manner to eight epoxyeicosatrienoic acids (EETs). Various EETs have been detected in the liver, as well as in many extrahepatic tissues, and have been implicated in numerous physiological funct...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425250902932923
更新日期:2009-07-01 00:00:00
abstract:INTRODUCTION:Treatments for hepatitis C virus (HCV) infection have advanced rapidly in the last decade. Pegylated interferon alpha 2a (PEG-IFN alpha 2a) alone, in combination with ribavirin and with or without direct acting antivirals (DAAs) is modestly effective in the treatment of chronic HCV infection. Areas covered...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2018.1421173
更新日期:2018-02-01 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:INTRODUCTION:Type 2 diabetes often involves derangements in lipid levels in addition to insulin resistance and diminishing insulin secretion. Colesevelam hydrochloride, a bile acid sequestrant (BAS), is approved for adjunctive therapy to diet and exercise for glycemic control in type 2 diabetes. In clinical studies in ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2012.672973
更新日期:2012-04-01 00:00:00
abstract:BACKGROUND:Testosterone replacement therapy in hypogonadal men has been used for > 60 years. The use of testosterone substitution is continuously growing and is given to aging men to improve the quality of life. Because testosterone use is associated with muscle strength enhancing effects, it has become a popular drug ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425250902976862
更新日期:2009-07-01 00:00:00
abstract:INTRODUCTION:Unacceptable failure rates in clinical trials are largely responsible for the high costs of bringing successful drugs to market - costs that are passed on to patients, insurers or healthcare providers. Furthermore, failures in clinical trials deny patients much-needed new drugs and potentially expose them ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2013.802770
更新日期:2013-09-01 00:00:00
abstract::Antithrombotic therapy is a crucial component of interventional cardiology and currently involves the administration of both anticoagulant and antiplatelet agents. The implementation of standard dual or triple antiplatelet therapies has allowed percutaneous coronary intervention (PCI) with stent implantation to become...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425225.3.4.609
更新日期:2007-08-01 00:00:00
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 we...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章
doi:10.1517/17425255.2013.802306
更新日期:2013-08-01 00:00:00
abstract:INTRODUCTION:Neonatal patients, because of the inability of their immune system to properly respond to microbial challenge, are highly susceptible to viral infections. Immunoglobulins, monoclonal antibody and antiviral drugs are used for prophylaxis and treatment of viral diseases in neonates. Neonates and, especially,...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.1108963
更新日期:2015-01-01 00:00:00
abstract:INTRODUCTION:Luteinizing hormone-releasing hormone agonists such as leuprolide acetate (LA) are the most frequently utilized treatment of advanced prostate cancer as the regimen for achieving androgen deprivation therapy (ADT). The efficacy of LA is determined by extent of testosterone (T) suppression in prostate cance...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.1073711
更新日期:2015-01-01 00:00:00
abstract::Acute kidney injury is a common condition and is associated with a high mortality rate. It has been recognised that routinely used measures of renal function, such as levels of blood urea nitrogen and serum creatinine, increase significantly only after substantial kidney injury occurs and then with a time delay. Insen...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2.5.697
更新日期:2006-10-01 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:INTRODUCTION:Pharmacokinetic and pharmacodynamic drug interactions (DIs) can occur between antiepileptics (AEDs) and second-generation antipsychotics (SGAPs). Some AED and SGAP pharmacodynamic mechanisms are poorly understood. AED-SGAP combinations are used for treating comorbid illnesses or increasing efficacy, partic...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2012.660918
更新日期:2012-03-01 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::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:Donepezil is a highly selective acetylcholinesterase inhibitor and one of the only four drugs currently approved for treatment of Alzheimer's dementia. Providing high bioavailability and a very long half-time, donepezil is regarded as effective and well tolerable in Alzheimer's disease patients, even in di...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2014.915028
更新日期:2014-07-01 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: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:Pregabalin is an alternative compound to SSRIs and SNRIs for the first-line treatment of generalized anxiety disorder (GAD). Areas covered: We describe the pharmacokinetic properties of pregabalin and their implications for the treatment of GAD. A search in the main database sources (Medline, ISI, Web of K...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2017.1281247
更新日期:2017-03-01 00:00:00
abstract:INTRODUCTION:Sepsis remains a leading cause of death worldwide. Despite years of extensive research, effective drugs that inhibit the pro-inflammatory effects of lipopolysaccharide (LPS) and improve outcome when added to conventional sepsis treatments are lacking. Eritoran tetrasodium (E5564) is a promising candidate t...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.558190
更新日期:2011-04-01 00:00:00
abstract:INTRODUCTION:Chronic hepatitis C virus (HCV) infection has recently become a curable disease with antiviral therapy. The knowledge of drug interactions using direct-acting antivirals (DAA) may permit maximizing antiviral efficacy and avoiding drug-related toxicities. Ageing in the chronic hepatitis C population, along ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.998997
更新日期:2015-03-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:There has been much interest in generating gene signatures to predict treatment response in breast cancer. AREAS COVERED IN THIS REVIEW:There are at least 15 published studies that describe baseline tumor gene signatures predicting chemotherapy sensitivity. As an extension of these baseline stu...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425250903510611
更新日期:2010-03-01 00:00:00
abstract:INTRODUCTION:Membrane transport proteins play a central role in regulating the disposition of endobiotics, dietary nutrients and environmental toxins. The inhibition of transporters by drugs has potential physiologic consequences. The full extent of the effect of drugs on the function of transporters is poorly understo...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2017.1372425
更新日期:2017-10-01 00:00:00
abstract:INTRODUCTION:Bioaccessibility is a growing area of research in the field of risk assessment. As polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants, they are the toxicants of focus to establish cancer risks in humans. Orally ingested PAHs also cause toxicity and even affect the pharmacokinet...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2013.823157
更新日期:2013-11-01 00:00:00