Abstract:
BACKGROUND:Methotrexate (MTX) is a folate analogue with high therapeutic efficiency in the treatment of cancers and autoimmune diseases. The efficacy and toxicity of MTX may be altered by genetic polymorphisms in genes involved in MTX metabolic pathway. Personalized pharmacotherapy based on gene polymorphisms enables a more efficient, compatible and cost-effective treatment of patients. OBJECTIVE:The present article aims to review genetic polymorphisms associated with MTX pharmacokinetics, toxicity, and outcome, and points out future development directions of individualized MTX therapy. METHODS:Details regarding the pharmacogenetics and pharmacogenomics of MTX are obtained from PubMed literatures. CONCLUSION:The influences of single nucleotide polymorphisms (SNPs) in genes involved in MTX pathway are controversial. Many pharmacogenetic associations are disease specific and race specific. Present studies have almost limited to some certain ethnic groups and diseases. The data from these studies are not convincing enough to draw far-reaching conclusions about the applicability of MTX pharmacogenetics in clinical practice. Studies with large scale and multiple centers are needed in the future. MTX-PG inhibits folic metabolism through three mechanisms. TS, MTHFR and ATIC are the rate-limiting enzymes separately. The function of SNPs in these genes is often onesided. Works focusing on the analysis of polymorphism in MTX transporters should be more efficient and meaningful.
journal_name
Curr Drug Metabjournal_title
Current drug metabolismauthors
Cao M,Guo M,Wu DQ,Meng Ldoi
10.2174/1389200219666171227201047subject
Has Abstractpub_date
2018-01-01 00:00:00pages
1182-1187issue
14eissn
1389-2002issn
1875-5453pii
CDM-EPUB-87580journal_volume
19pub_type
杂志文章,评审abstract:BACKGROUND:Gold nanoparticles have been exploited for nanobiotechnology applications for the last two decades. New insights of the nanomaterials as promising agent for cancer diagnosis and therapy have just started to emerge. Due to the size- and shape-dependent optical, electrical and thermal properties, gold nanopart...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200218666170925122513
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Overactive bladder syndrome is a broadly occurring urological disorder with a distressing impact on the quality of life. The commonly used antimuscarinic drugs show poor patient compliance because of unsatisfactory potency, tolerability and high occurrence of adverse effects such as dry mouth, blurred vision...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200221666200425211139
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journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/138920010794328913
更新日期:2010-11-01 00:00:00
abstract::The occurrence of idiosyncratic adverse drug reactions during late clinical trials or after a drug has been released can lead to a severe restriction in its use and even in its withdrawal. Metabolic activation of relatively inert functional groups to reactive electrophilic intermediates is considered to be an obligato...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200054021799
更新日期:2005-06-01 00:00:00
abstract::The pharmacological effects of a drug are highly dependent on the absorption, metabolism, elimination, and distribution of the drug. In the past few years it has become apparent that transport proteins play a major role in regulating the distribution, elimination and metabolism of some drugs. As a consequence of our n...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200023337559
更新日期:2002-06-01 00:00:00
abstract::Personalized medicine has gained significant attention over the last decade as technologies for understanding biological differences between individuals have advanced dramatically. There are many potential benefits of personalized medicine including minimizing risk of drug toxicity, increasing benefit from drugs used,...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920012802138615
更新日期:2012-09-01 00:00:00
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journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200217666160607232540
更新日期:2016-01-01 00:00:00
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journal_title:Current drug metabolism
pub_type: 杂志文章,评审
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更新日期:2011-12-01 00:00:00
abstract:BACKGROUND:Drug-metabolizing enzymes and transporters play key roles in drug disposition and drug interactions. The alterations of their expression will influence drug pharmacokinetics and pharmacodynamics. However, the changes in the expression of enzymes and transporters in the disease state are still unclear. OBJEC...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/1389200221666200512113731
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Bioequivalence studies are a vital part of drug development. The average bioequivalence approach is the standard method of assessment to conclude whether the generic product is bioequivalent to the innovator product. Of late, debates are on whether the average bioequivalence approach adequately addresses dru...
journal_title:Current drug metabolism
pub_type: 杂志文章,随机对照试验
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更新日期:2020-01-01 00:00:00
abstract::Modern biologics are biotechnology-derived pharmaceuticals. They are mostly used for diagnosis, prevention and treatment of serious and chronic diseases. Today, therapeutic biologics range from traditional biologics like blood and blood components, fractionated blood products, and antitoxins to modern biologics such a...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
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更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:ET-26 hydrochloride is a novel intravenous anesthetic, approved for clinical trials, that produces a desirable sedative-hypnotic effect with stable myocardial performance and mild adrenocortical suppression in rats and beagle dogs. The objective of this study was to assess the absorption, distribution, metab...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/1389200221666191223105504
更新日期:2019-01-01 00:00:00
abstract::The combined treatment with anticonvulsant and antidepressant drugs is reported in both neurologic and psychiatric practice; it is, therefore, evident that the issue of managing such type of polytherapy is frequently encountered by clinicians. To review current literature on pharmacokinetic interactions between antico...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920008786049311
更新日期:2008-10-01 00:00:00
abstract::Understanding the mechanism of action of organophosphates (OP)/nerve agents -- irreversible acetylcholinesterase (AChE, EC 3.1.1.7) inhibition at the cholinergic synapses followed by metabolic dysbalance of the organism -- two therapeutic principles for antidotal treatment are derived. The main drugs are anticholinerg...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/138920007782798144
更新日期:2007-12-01 00:00:00
abstract::Glucuronidation is responsible for the clearance of a diverse range of drug and chemicals whose topology confers properties that complicate in vitro-in vivo clearance correlations as compared to those possible for oxidative metabolism. The active site of the UGTs faces the inside of the luminal space of the endoplasmi...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200023336992
更新日期:2002-12-01 00:00:00
abstract::New chemical entities are routinely screened in vitro and in vivo for their ability to induce cytochrome P450s (CYP), other drug-metabolizing enzymes and possibly transporters in an attempt to more accurately predict clinical parameters such as drug-drug interactions and clearance in humans. Some of these potential th...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200033489352
更新日期:2003-10-01 00:00:00
abstract:BACKGROUND:The metabolic/biotransformation pathways of atypical antipsychotics (aripiprazole, clozapine, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone) have been characterized and reviewed. However, comparisons of excretory pathways remain unexplored. OBJECTIVE:To analyze the excretio...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920010791636202
更新日期:2010-07-01 00:00:00
abstract::5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) belongs to a group of naturally-occurring psychoactive indolealkylamine drugs. It acts as a nonselective serotonin (5-HT) agonist and causes many physiological and behavioral changes. 5-MeO-DMT is O-demethylated by polymorphic cytochrome P450 2D6 (CYP2D6) to an active metab...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920010794233495
更新日期:2010-10-01 00:00:00
abstract::Arylamine N-acetyltransferases (NAT) are xenobiotic-metabolizing enzymes responsible for the acetylation of many aromatic arylamine and heterocyclic amines, thereby playing an important role in both detoxification and activation of numerous drugs and carcinogens. Two closely related isoforms (NAT1 and NAT2) have been ...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
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更新日期:2008-07-01 00:00:00
abstract:BACKGROUND:Medical application of nanotechnology is termed as Nanomedicine and is widely used in healthcare industries. Nanotechnology has helped Physicians, Scientists and Technologists to understand the changes in cellular levels to develop nanomedicines and address the challenges faced by the healthcare sectors. Nan...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
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更新日期:2018-01-01 00:00:00
abstract::This review focuses on identification of the important active site residues of CYP2D6 in terms of CYP2D6 polymorphism. A meta-analysis was performed on the reported literature regarding (1) values of the Michaelis-Menten constant (K(m)), maximal velocity (V(max)), and intrinsic clearance (V(max)/K(m)) for 41 metabolic...
journal_title:Current drug metabolism
pub_type: 杂志文章,meta分析,评审
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更新日期:2011-06-01 00:00:00
abstract::A amyloid-β (Aβ) plaque formation in the brain is known to be the root cause of Alzheimer's disease (AD), which affects the behavior, memory, and cognitive ability in humans. The brain starts undergoing changes several years before the actual appearance of the symptoms. Nanotechnology could prove to be an alternative ...
journal_title:Current drug metabolism
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更新日期:2020-01-01 00:00:00
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journal_title:Current drug metabolism
pub_type: 杂志文章,评审
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更新日期:2013-10-01 00:00:00
abstract::For the pharmaceutical industry, one of the challenges in evaluating the risk of future compound attrition at the discovery stage is the successful prediction of the major routes of clearance in humans. For compounds cleared by metabolism, such information will help to avoid the development of compounds that will exhi...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
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更新日期:2003-12-01 00:00:00
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journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920012798918426
更新日期:2012-02-01 00:00:00
abstract:BACKGROUND:The red-crowned crane (Grus japonensis) is one of the most vulnerable bird species in the world. Mycotoxins are toxic secondary metabolites produced by fungi and considered naturally unavoidable contaminants in animal feed. Our recent survey indicated that the mycotoxins had the potential to contaminate redc...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/1389200221666200726221126
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Kidney dysfunction resulting from various drugs is an important issue during the drug development process. Traditional in vivo animal experiments are limited with respect to evaluating drug efficacy and nephrotoxicity due to discrepancies in drug pharmacokinetics and pharmacodynamics between humans and anima...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200219666180309101844
更新日期:2018-01-01 00:00:00
abstract::Ophthalmic drugs are delivered to ocular tissues predominantly via relatively simple formulations, such as topically dosed water-soluble drug solutions and water-insoluble drug suspensions in ointments. An ideal topical drug delivery system should possess certain desirable properties, such as good corneal and conjunct...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
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更新日期:2007-02-01 00:00:00
abstract::Infection with the human immunodeficiency virus type 1 (HIV) results in a chronic infection that progressively cripples the host immune defenses. HIV infection is associated with increased tryptophan (trp) catabolism by the cytokine-inducible enzyme indoleamine 2,3-dioxygenase (IDO). IDO has powerful immune suppressiv...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
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更新日期:2007-04-01 00:00:00
abstract:BACKGROUND:Painful peripheral neuropathy is a dose-limiting adverse effect of the antitumor drug oxaliplatin. The main symptoms of neuropathy: tactile allodynia and cold hyperalgesia, appear in more than 80% of patients on oxaliplatin therapy and are due to the overexpression of neuronal sodium channels (Navs) and neur...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/1389200221666200711155632
更新日期:2020-01-01 00:00:00