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
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 |
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剂型
Form | Route | Strength |
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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 |
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Substructures |
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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 |
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Protein binding | 50%, primarily to albumin | ||||||
Metabolism |
Hepatic. |
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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 |
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Pathways |
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理化性质
Properties | |||||||||||||||||||||||||||||||||||||
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State | solid | ||||||||||||||||||||||||||||||||||||
Melting point | 195 oC | ||||||||||||||||||||||||||||||||||||
Experimental Properties |
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Predicted Properties |
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药物相互作用
Drug | Interaction |
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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.