用户名： 密   码：
注册 | 忘记密码？
药品详细

Methotrexate (甲氨蝶呤 )

化学结构式图
中文名
甲氨蝶呤
英文名
Methotrexate
分子式
Not Available
化学名
(2S)-2-[(4-{[(2,4-diaminopteridin-6-yl)methyl](methyl)amino}phenyl)formamido]pentanedioic acid
分子量
Average: 454.4393
Monoisotopic: 454.171315854
CAS号
59-05-2
ATC分类
L01B 抗代谢药;L04A 未知
药物类型
small molecule
阶段
商品名
Abitrexate;Antifolan;Arbitrexate;Emtexate;Folex;Ledertrexate;Metatrexan;Methotrate;Mexate;Rheumatrex;Trexall;
同义名
Amethopterin;Amethopterine;HDMTX;L-Amethopterin;Methopterin;Methotextrate;Methotrexat;Methotrexate Sodium;Methylaminopterin;Methylaminopterinum;MTX;N-Bismethylpteroylglutamic Acid;
基本介绍

An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of tetrahydrofolate dehydrogenase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [PubChem]

生产厂家
  • Abic ltd
  • Abraxis pharmaceutical products
  • App pharmaceuticals llc
  • Barr laboratories inc
  • Bedford laboratories div ben venue laboratories inc
  • Bioniche pharma usa llc
  • Bristol laboratories inc div bristol myers co
  • Bristol myers co
  • Bristol myers squibb
  • Dava pharmaceuticals inc
  • Duramed pharmaceuticals inc sub barr laboratories inc
  • Ebewe pharma ges mbh nfg kg
  • Hospira inc
  • Mylan pharmaceuticals inc
  • Norbrook laboratories ltd
  • Pharmachemie bv
  • Pharmachemie usa inc
  • Pharmacia and upjohn co
  • Roxane laboratories inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Klareskog L, van der Heijde D, de Jager JP, Gough A, Kalden J, Malaise M, Martin Mola E, Pavelka K, Sany J, Settas L, Wajdula J, Pedersen R, Fatenejad S, Sanda M: Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet. 2004 Feb 28;363(9410):675-81. Pubmed
  2. Johnston A, Gudjonsson JE, Sigmundsdottir H, Ludviksson BR, Valdimarsson H: The anti-inflammatory action of methotrexate is not mediated by lymphocyte apoptosis, but by the suppression of activation and adhesion molecules. Clin Immunol. 2005 Feb;114(2):154-63. Pubmed
剂型
Form Route Strength
Solution Intramuscular
Solution Intrathecal
Solution Intravenous
Tablet Oral
规格
Unit description Cost Unit
Methotrexate powder 261.33 USD g
Rheumatrex 8 2.5 mg tablet Disp Pack 169.98 USD disp
Rheumatrex 24 2.5 mg tablet Disp Pack 129.06 USD disp
Rheumatrex 20 2.5 mg tablet Disp Pack 107.59 USD disp
Rheumatrex 12 2.5 mg tablet Disp Pack 63.65 USD disp
Methotrexate Sodium 25 mg/ml (pf) Solution 40ml Vial 58.99 USD vial
Trexall 15 mg tablet 25.98 USD tablet
Methotrexate Sodium 25 mg/ml (pf) Solution 10ml Vial 24.99 USD vial
Trexall 10 mg tablet 17.67 USD tablet
Methotrexate Sodium 25 mg/ml Solution 1 Vial = 2ml 15.11 USD vial
Methotrexate Sodium 25 mg/ml (pf) Solution 2ml Vial 14.99 USD vial
Trexall 7.5 mg tablet 12.99 USD tablet
Rheumatrex 2.5 mg tablet 11.23 USD tablet
Trexall 5 mg tablet 8.66 USD tablet
Methotrexate Sod. (Preserved) 25 mg/ml 8.38 USD ml
Methotrexate Sod.(Unpreserved) 25 mg/ml 4.56 USD ml
Methotrexate 2.5 mg tablet 2.71 USD tablet
Methotrexate 10 mg Tablet 2.58 USD tablet
Ratio-Methotrexate Sodium 2.5 mg Tablet 0.66 USD tablet
Apo-Methotrexate 2.5 mg Tablet 0.66 USD tablet
化合物类型
Type small molecule
Classes
  • Pterins
  • Keto-Acids
Substructures
  • Pterins
  • Hydroxy Compounds
  • Acetates
  • Amino Ketones
  • Aliphatic and Aryl Amines
  • Benzene and Derivatives
  • Carboxylic Acids and Derivatives
  • Pyrimidines and Derivatives
  • Pyrazines
  • Heterocyclic compounds
  • Aromatic compounds
  • Keto-Acids
  • Carboxamides and Derivatives
  • Pteridines
  • Imines
  • Benzoyl Derivatives
  • Cyanamides
  • Benzamides
  • Anilines
适应症
Cancer 癌症;IMMUNOSUPPRESSIVE 免疫抑制;
药理
Indication For the treatment of gestational choriocarcinoma, chorioadenoma destruens and hydatidiform mole. Also for the treatment of severe psoriasis and severe, active, classical or definite rheumatoid arthritis.
Pharmacodynamics Methotrexate is an antineoplastic anti-metabolite. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. Methotrexate inhibits folic acid reductase which is responsible for the conversion of folic acid to tetrahydrofolic acid. At two stages in the biosynthesis of purines and at one stage in the synthesis of pyrimidines, one-carbon transfer reactions occur which require specific coenzymes synthesized in the cell from tetrahydrofolic acid. Tetrahydrofolic acid itself is synthesized in the cell from folic acid with the help of an enzyme, folic acid reductase. Methotrexate looks a lot like folic acid to the enzyme, so it binds to it quite strongly and inhibits the enzyme. Thus, DNA synthesis cannot proceed because the coenzymes needed for one-carbon transfer reactions are not produced from tetrahydrofolic acid because there is no tetrahydrofolic acid. Methotrexate selectively affects the most rapidly dividing cells (neoplastic and psoriatic cells). Methotrexate is also indicated in the management of severe, active, classical, or definite rheumatoid arthritis.
Mechanism of action Methotrexate anti-tumor activity is a result of the inhibition of folic acid reductase, leading to inhibition of DNA synthesis and inhibition of cellular replication. The mechanism involved in its activity against rheumatoid arthritis is not known.
Absorption Generally well absorbed with a mean bioavailability of about 60%.
Volume of distribution
  • 0.4 to 0.8 L/kg
Protein binding 50%, primarily to albumin
Metabolism

Hepatic.
Route of elimination With IV administration, 80% to 90% of the administered dose is excreted unchanged in the urine within 24 hours. There is limited biliary excretion amounting to 10% or less of the administered dose.
Half life Low doses: 3 to 10 hours; High doses: 8 to 15 hours.
Clearance Not Available
Toxicity Symptoms of overdose include bone marrow suppression and gastrointestinal toxicity. LD50=43mg/kg(orally in rat).
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00432 Methotrexate Pathway SMP00432
理化性质
Properties
State solid
Melting point 195 oC
Experimental Properties
Property Value Source
water solubility 2600 mg/L PhysProp
logP -2.2 PhysProp
Caco2 permeability -5.92 [ADME Research, USCD] BiGG
pKa 4.7 Various sources
Predicted Properties
Property Value Source
water solubility 1.71e-01 g/l ALOGPS
logP -0.91 ALOGPS
logP -0.51 ChemAxon Molconvert
logS -3.42 ALOGPS
pKa 4.14 ChemAxon Molconvert
hydrogen acceptor count 12 ChemAxon Molconvert
hydrogen donor count 5 ChemAxon Molconvert
polar surface area 210.54 ChemAxon Molconvert
rotatable bond count 9 ChemAxon Molconvert
refractivity 119.21 ChemAxon Molconvert
polarizability 44.54 ChemAxon Molconvert
药物相互作用
Drug Interaction
Acetylsalicylic acid Acetylsalicylic acid increases the effect and toxicity of methotrexate.
Acitretin Acitretin/etretinate increases the effect and toxicity of methotrexate
Amoxicillin The penicillin increases the effect and toxicity of methotrexate
Ampicillin The penicillin increases the effect and toxicity of methotrexate
Bacampicillin The penicillin increases the effect and toxicity of methotrexate
Bismuth Subsalicylate The salicylate, bismuth subsalicylate, increases the effect and toxicity of methotrexate.
Carbenicillin The penicillin increases the effect and toxicity of methotrexate
Cholestyramine Decreased levels of methotrexate
Ciprofloxacin Ciprofloxacine may decrease the metabolism of methotrexate. Monitor for changes adverse effects of methotrexate if ciprofloxacin is initiated.
Cisplatin Cisplatin increases methotrexate toxicity
Clavulanate The penicillin increases the effect and toxicity of methotrexate
Cloxacillin The penicillin increases the effect and toxicity of methotrexate
Cyclosporine Cyclosporine may increase the effect and toxicity of methotrexate.
Diclofenac The NSAID, diclofenac, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Dicloxacillin The penicillin increases the effect and toxicity of methotrexate
Diflunisal The NSAID, diflunisal, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Digoxin The antineoplasic agent decreases the effect of digoxin
Doxycycline The tetracycline, doxycycline, may increase methotrexate toxicity.
Ethotoin The antineoplasic agent decreases the effect of hydantoin
Etodolac The NSAID, etodolac, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Etretinate Acitretin/etretinate increases the effect and toxicity of methotrexate
Fenoprofen The NSAID, fenoprofen, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Flucloxacillin The penicillin increases the effect and toxicity of methotrexate
Flurbiprofen The NSAID, flurbiprofen, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Fosphenytoin The antineoplasic agent decreases the effect of hydantoin
Hydroxychloroquine Hydroxychloroquine increases the effect and toxicity of methotrexate
Ibuprofen The NSAID, ibuprofen, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Indomethacin The NSAID, indomethacin, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Ketoprofen The NSAID, ketoprofen, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Ketorolac The NSAID, ketorolac, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Magnesium salicylate The salicylate, magnesium salicylate, increases the effect and toxicity of methotrexate.
Meclofenamic acid The NSAID, meclofenamic acid, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Mefenamic acid The NSAID, mefenamic acid, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Mephenytoin The antineoplasic agent decreases the effect of hydantoin
Methicillin Acyl-Serine The penicillin increases the effect and toxicity of methotrexate
Mezlocillin The penicillin increases the effect and toxicity of methotrexate
Nabumetone The NSAID, nabumetone, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Nafcillin The penicillin increases the effect and toxicity of methotrexate
Naproxen The NSAID, naproxen, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Omeprazole Omeprazole increases the levels of methotrexate
Oxaprozin The NSAID, oxaprozin, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Penicillin G The penicillin increases the effect and toxicity of methotrexate
Penicillin V The penicillin increases the effect and toxicity of methotrexate
Phenylbutazone The NSAID, phenylbutazone, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Phenytoin The antineoplasic agent decreases the effect of hydantoin
Piperacillin The penicillin increases the effect and toxicity of methotrexate
Piroxicam The NSAID, piroxicam, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Pivampicillin The penicillin increases the effect and toxicity of methotrexate
Probenecid Probenecid increases the effect and toxicity of methotrexate
Procarbazine Increased nephrotoxicity with this combination
Rofecoxib Rofecoxib increases the levels of methotrexate
Salicylate-sodium The salicylate, salicylate-sodium, increases the effect and toxicity of methotrexate.
Salsalate The salicylate, salsalate, increases the effect and toxicity of methotrexate.
Sulfacytine The sulfamide increases the toxicity of methotrexate
Sulfadiazine The sulfamide increases the toxicity of methotrexate
Sulfadimethoxine The sulfamide increases the toxicity of methotrexate
Sulfadoxine The sulfamide increases the toxicity of methotrexate
Sulfamerazine The sulfamide increases the toxicity of methotrexate
Sulfamethazine The sulfamide increases the toxicity of methotrexate
Sulfamethizole The sulfamide increases the toxicity of methotrexate
Sulfamethoxazole The sulfamide increases the toxicity of methotrexate
Sulfapyridine The sulfamide increases the toxicity of methotrexate
Sulfathiazole The sulfamide increases the toxicity of methotrexate
Sulfisoxazole The sulfamide increases the toxicity of methotrexate
Sulindac The NSAID, sulindac, may decrease the clearance methotrexate. Consider alternate therapy, especially in patients receiving high antineoplastic doses of methotrexate. Otherwise, monitor for hematologic and renal toxicities.
Tenoxicam Tenoxicam may increase the serum concentration of Methotrexate by reducing renal tubular secretion of Methotrexate. Monitor for changes in Methotrexate therapeutic and adverse effects if Tenoxicam is initiated, discontinued or dose changed.
Tetracycline Tetracycline may increase methotrexate toxicity.
Tiaprofenic acid Tiaprofenic acid may decrease renal excretion of methotrexate. Consider alternate therapy or monitor for methotrexate toxicity.
Ticarcillin The penicillin increases the effect and toxicity of methotrexate
Tolmetin Tolmetin may decrease the renal excretion of Methotrexate. Alternate therapy should be considered. Otherwise, monitor for hemotologic and renal toxicities.
Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Trimethoprim Trimethoprim may increase the adverse/toxic effects of Methotrexate (e.g. bone marrow suppression). Concomitant use should be avoided or closely monitored for Methotrexate toxicity.
Trisalicylate-choline The salicylate, trisalicylate-choline, increases the effect and toxicity of methotrexate.
食物相互作用
  • Milk appears to reduce its absorption.
  • Take without regard to meals. Limit caffeine intake.

返回 | 收藏