Pharmacogenomics of Methotrexate: Current Status and Future Outlook.

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 Metab

journal_title

Current drug metabolism

authors

Cao M,Guo M,Wu DQ,Meng L

doi

10.2174/1389200219666171227201047

subject

Has Abstract

pub_date

2018-01-01 00:00:00

pages

1182-1187

issue

14

eissn

1389-2002

issn

1875-5453

pii

CDM-EPUB-87580

journal_volume

19

pub_type

杂志文章,评审
  • Gold Nanoparticles: Promising Agent to Improve the Diagnosis and Therapy of Cancer.

    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

    authors: Ning L,Zhu B,Gao T

    更新日期:2017-01-01 00:00:00

  • Potential of Mirabegron and its Extended-release Formulations for the Treatment of Overactive Bladder Syndrome.

    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

    authors: Mandpe P,Prabhakar B,Shende P

    更新日期:2020-01-01 00:00:00

  • Interplay of metabolism and transport in determining oral drug absorption and gut wall metabolism: a simulation assessment using the "Advanced Dissolution, Absorption, Metabolism (ADAM)" model.

    abstract::Bioavailability of orally administered drugs can be influenced by a number of factors including release from the formulation, dissolution, stability in the gastrointestinal (GI) environment, permeability through the gut wall and first-pass gut wall and hepatic metabolism. Although there are various enzymes in the gut ...

    journal_title:Current drug metabolism

    pub_type: 杂志文章

    doi:10.2174/138920010794328913

    authors: Darwich AS,Neuhoff S,Jamei M,Rostami-Hodjegan A

    更新日期:2010-11-01 00:00:00

  • A comprehensive listing of bioactivation pathways of organic functional groups.

    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

    authors: Kalgutkar AS,Gardner I,Obach RS,Shaffer CL,Callegari E,Henne KR,Mutlib AE,Dalvie DK,Lee JS,Nakai Y,O'Donnell JP,Boer J,Harriman SP

    更新日期:2005-06-01 00:00:00

  • Evaluation of drug interactions with P-glycoprotein in drug discovery: in vitro assessment of the potential for drug-drug interactions with P-glycoprotein.

    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

    authors: Hochman JH,Yamazaki M,Ohe T,Lin JH

    更新日期:2002-06-01 00:00:00

  • Personalized medicine: potential, barriers and contemporary issues.

    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

    authors: Sorich MJ,McKinnon RA

    更新日期:2012-09-01 00:00:00

  • Recent Developments of Magnetic Nanoparticles for Theranostics of Brain Tumor.

    abstract:BACKGROUND:Glioblastoma multiforme, one of the most aggressive brain tumors, has a very poor clinical outcome. Despite the introduction of the alkylating reagent temozolomide (TMZ) to surgery and radiotherapy, the survival of patients could only be modestly increased up to less than 15 months. Therefore, innovative tre...

    journal_title:Current drug metabolism

    pub_type: 杂志文章,评审

    doi:10.2174/1389200217666160607232540

    authors: Shevtsov M,Multhoff G

    更新日期:2016-01-01 00:00:00

  • Pharmacokinetic and metabolism determinants of fluoropyrimidines and oxaliplatin activity in treatment of colorectal patients.

    abstract::Fluoropyrimidines and oxaliplatin continued to be the mainstay of therapeutic regimens in the treatment of colorectal cancer (CRC). For this reason, pharmacokinetic and metabolism of these drugs were analyzed and the identification of accurate and validated predictive, prognostic and toxicity markers became necessary ...

    journal_title:Current drug metabolism

    pub_type: 杂志文章,评审

    doi:10.2174/138920011798062300

    authors: Gnoni A,Russo A,Silvestris N,Maiello E,Vacca A,Marech I,Numico G,Paradiso A,Lorusso V,Azzariti A

    更新日期:2011-12-01 00:00:00

  • Changes of Transporters and Drug-metabolizing Enzymes in Nephrotic Syndrome.

    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

    authors: Dong Y,Gong L,Lu X,Ye M,Lin Y,Xie S,Zhang J,Zhou F,Tang L,Zou W,Liu M

    更新日期:2020-01-01 00:00:00

  • Has the Time Come to Employ Population and Individual Bioequivalence for the Evaluation of Generics?

    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

    doi:10.2174/1389200221666200401105119

    authors: Micheal F,Sayana M,Prasad R,Motilal BM

    更新日期:2020-01-01 00:00:00

  • Early development of therapeutic biologics--pharmacokinetics.

    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

    doi:10.2174/138920006774832604

    authors: Baumann A

    更新日期:2006-01-01 00:00:00

  • Preclinical Pharmacokinetics Study of a Novel Intravenous Anesthetic ET-26 Hydrochloride.

    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

    authors: Zhang YJ,Deng C,Yang J,Gong D,Kang Y,Liu J,Zhang W

    更新日期:2019-01-01 00:00:00

  • Anticonvulsants - antidepressants pharmacokinetic drug interactions: the role of the CYP450 system in psychopharmacology.

    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

    authors: Mula M

    更新日期:2008-10-01 00:00:00

  • Cholinesterase reactivators: the fate and effects in the organism poisoned with organophosphates/nerve agents.

    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

    authors: Bajgar J,Kuca K,Jun D,Bartosova L,Fusek J

    更新日期:2007-12-01 00:00:00

  • Complexities of glucuronidation affecting in vitro in vivo extrapolation.

    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

    authors: Lin JH,Wong BK

    更新日期:2002-12-01 00:00:00

  • Prediction of human drug metabolizing enzyme induction.

    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

    authors: Mankowski DC,Ekins S

    更新日期:2003-10-01 00:00:00

  • Atypical antipsychotic metabolism and excretion.

    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

    authors: Sheehan JJ,Sliwa JK,Amatniek JC,Grinspan A,Canuso CM

    更新日期:2010-07-01 00:00:00

  • Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions.

    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

    authors: Shen HW,Jiang XL,Winter JC,Yu AM

    更新日期:2010-10-01 00:00:00

  • Effect of environmental substances on the activity of arylamine N-acetyltransferases.

    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

    doi:10.2174/138920008784892092

    authors: Rodrigues-Lima F,Dairou J,Dupret JM

    更新日期:2008-07-01 00:00:00

  • Pharmacokinetics, Metabolism, Distribution and Permeability of Nanomedicine.

    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

    doi:10.2174/1389200219666180305154119

    authors: Ravindran S,Suthar JK,Rokade R,Deshpande P,Singh P,Pratinidhi A,Khambadkhar R,Utekar S

    更新日期:2018-01-01 00:00:00

  • Comparison of cytochrome P450 2D6 and variants in terms of drug oxidation rates and substrate inhibition.

    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

    doi:10.2174/138920011795495286

    authors: Niwa T,Murayama N,Yamazaki H

    更新日期:2011-06-01 00:00:00

  • Recent Advances in Nanotechnology: A Novel Therapeutic System for the Treatment of Alzheimer's Disease.

    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

    pub_type: 杂志文章

    doi:10.2174/1389200221666201124140518

    authors: Chauhan PS,Yadav D,Koul B,Mohanta YK,Jin JO

    更新日期:2020-01-01 00:00:00

  • Review of and perspectives on the toxicology of graphene-based materials.

    abstract::Graphene possesses a wide range of potential biomedical applications because of the unique physical and chemical properties. However, the side effects of grapheme and its derivatives on a number of biological models even on human body are still not very clear. Therefore, to properly assess the potential risk of graphe...

    journal_title:Current drug metabolism

    pub_type: 杂志文章,评审

    doi:10.2174/138920021131400108

    authors: Xu C,Wang J,Xu Y,Shang G,Wang R,Lin Y

    更新日期:2013-10-01 00:00:00

  • Reaction phenotyping in drug discovery: moving forward with confidence?

    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

    doi:10.2174/1389200033489235

    authors: Williams JA,Hurst SI,Bauman J,Jones BC,Hyland R,Gibbs JP,Obach RS,Ball SE

    更新日期:2003-12-01 00:00:00

  • Liver-based in vitro technologies for drug biotransformation studies - a review.

    abstract::Early understanding of the metabolic pathway and potential interaction of new drug candidates with other drugs is one of the goals of preclinical studies in the drug discovery process. Although other body organs are involved in drug biotransformation, the liver is the predominant organ of metabolism for a wide range o...

    journal_title:Current drug metabolism

    pub_type: 杂志文章,评审

    doi:10.2174/138920012798918426

    authors: Fasinu P,Bouic PJ,Rosenkranz B

    更新日期:2012-02-01 00:00:00

  • Effects of Montmorillonite on Growth Performance, Serum Biochemistry and Oxidative Stress of Red-Crowned Crane (Grus japonensis) Fed Mycotoxin-Contaminated Feed.

    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

    authors: Liu D,Wu Q,Liu H,Lu C,Gu C,Kuca K,Wu W

    更新日期:2020-01-01 00:00:00

  • Kidney-on-a-Chip: A New Technology for Predicting Drug Efficacy, Interactions, and Drug-induced Nephrotoxicity.

    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

    authors: Lee J,Kim S

    更新日期:2018-01-01 00:00:00

  • Ocular disposition, pharmacokinetics, efficacy and safety of nanoparticle-formulated ophthalmic drugs.

    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

    doi:10.2174/138920007779815977

    authors: Bu HZ,Gukasyan HJ,Goulet L,Lou XJ,Xiang C,Koudriakova T

    更新日期:2007-02-01 00:00:00

  • How does indoleamine 2,3-dioxygenase contribute to HIV-mediated immune dysregulation.

    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

    doi:10.2174/138920007780362527

    authors: Boasso A,Shearer GM

    更新日期:2007-04-01 00:00:00

  • Comparison of Bromhexine and its Active Metabolite - Ambroxol as Potential Analgesics Reducing Oxaliplatin-induced Neuropathic Pain - Pharmacodynamic and Molecular Docking Studies.

    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

    authors: Furgała-Wojas A,Kowalska M,Nowaczyk A,Fijałkowski Ł,Sałat K

    更新日期:2020-01-01 00:00:00