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       [Methotrexate]
  > [Methotrexate] CAS number/59-05-2 ATC code/L01BA01 L04AX03 PubChem/126941 DrugBank/APRD00353 Formula/C20H22N8O5 Mol. mass/454.44 g/mol Bioavailability/17–90% Metabolism/hepatic Excretion/renal 48–100% Pregnancy cat./
D(AU) X(US) Legal status/
Prescription Only (S4)(AU) POM(UK) ℞-only(US) Routes/oral, IV, IM, SC, intrathecal 
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    | Mechanism of Action | 
    
       Methotrexate¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ 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. 
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    | Pharmacology | 
     
       Methotrexate¿¡ ´ëÇÑ Pharmacology Á¤º¸ 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. 
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    | Metabolism | 
    
       Methotrexate¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Aldehyde oxidaseXanthine dehydrogenase/oxidaseMethylenetetrahydrofolate reductase 
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    | Absorption | 
    
       Methotrexate¿¡ ´ëÇÑ Absorption Á¤º¸ Generally well absorbed with a mean bioavailability of about 60%. 
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    | Toxicity | 
    
       Methotrexate¿¡ ´ëÇÑ Toxicity Á¤º¸ Symptoms of overdose include bone marrow suppression and gastrointestinal toxicity. LD50=43mg/kg(orally in rat). 
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    | Drug Interactions | 
    
       Methotrexate¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Acitretin	Acitretin/etretinate increases the effect and toxicity of methotrexateEtretinate	Acitretin/etretinate increases the effect and toxicity of methotrexateAmoxicillin	The penicillin increases the effect and toxicity of methotrexateAmpicillin	The penicillin increases the effect and toxicity of methotrexateBacampicillin	The penicillin increases the effect and toxicity of methotrexateCarbenicillin	The penicillin increases the effect and toxicity of methotrexateCiprofloxacin	Ciprofloxacin increases methotrexate toxicityCisplatin	Cisplatin increases methotrexate toxicityCloxacillin	The penicillin increases the effect and toxicity of methotrexateCyclosporine	Cyclosporine increases the effect and toxicity of methotrexateDicloxacillin	The penicillin increases the effect and toxicity of methotrexateFlucloxacillin	The penicillin increases the effect and toxicity of methotrexateMethicillin Acyl-Serine	The penicillin increases the effect and toxicity of methotrexateMezlocillin	The penicillin increases the effect and toxicity of methotrexateNafcillin	The penicillin increases the effect and toxicity of methotrexatePenicillin G	The penicillin increases the effect and toxicity of methotrexatePenicillin V	The penicillin increases the effect and toxicity of methotrexatePiperacillin	The penicillin increases the effect and toxicity of methotrexatePivampicillin	The penicillin increases the effect and toxicity of methotrexateTicarcillin	The penicillin increases the effect and toxicity of methotrexateTrimethoprim	Timethoprim increases methotrexate toxicityProcarbazine	Increased nephrotoxicity with this combinationRofecoxib	Rofecoxib increases the levels of methotrexateProbenecid	Probenecid increases the effect and toxicity of methotrexateOmeprazole	Omeprazole increases the levels of methotrexateHydroxychloroquine	Hydroxychloroquine increases the effect and toxicity of methotrexateAspirin	The salicylate increases the effect and toxicity of methotrexateBismuth Subsalicylate	The salicylate increases the effect and toxicity of methotrexateSalicylate-magnesium	The salicylate increases the effect and toxicity of methotrexateSalicylate-sodium	The salicylate increases the effect and toxicity of methotrexateSalsalate	The salicylate increases the effect and toxicity of methotrexateTrisalicylate-choline	The salicylate increases the effect and toxicity of methotrexateCholestyramine	Decreased levels of methotrexateDiclofenac	The NSAID increases the effect and toxicity of methotrexateEtodolac	The NSAID increases the effect and toxicity of methotrexateFenoprofen	The NSAID increases the effect and toxicity of methotrexateFlurbiprofen	The NSAID increases the effect and toxicity of methotrexateIbuprofen	The NSAID increases the effect and toxicity of methotrexateIndomethacin	The NSAID increases the effect and toxicity of methotrexateKetoprofen	The NSAID increases the effect and toxicity of methotrexateKetorolac	The NSAID increases the effect and toxicity of methotrexateMeclofenamic acid	The NSAID increases the effect and toxicity of methotrexateMefenamic acid	The NSAID increases the effect and toxicity of methotrexateNabumetone	The NSAID increases the effect and toxicity of methotrexateNaproxen	The NSAID increases the effect and toxicity of methotrexateOxaprozin	The NSAID increases the effect and toxicity of methotrexatePhenylbutazone	The NSAID increases the effect and toxicity of methotrexatePiroxicam	The NSAID increases the effect and toxicity of methotrexateSulindac	The NSAID increases the effect and toxicity of methotrexateTiaprofenic acid	The NSAID increases the effect and toxicity of methotrexateTolmetin	The NSAID increases the effect and toxicity of methotrexateDigoxin	The antineoplasic agent decreases the effect of digoxinEthotoin	The antineoplasic agent decreases the effect of hydantoinFosphenytoin	The antineoplasic agent decreases the effect of hydantoinMephenytoin	The antineoplasic agent decreases the effect of hydantoinPhenytoin	The antineoplasic agent decreases the effect of hydantoinDoxycycline	The tetracycline increases methotrexate toxicityTetracycline	The tetracycline increases methotrexate toxicitySulfacytine	The sulfamide increases the toxicity of methotrexateSulfadiazine	The sulfamide increases the toxicity of methotrexateSulfadoxine	The sulfamide increases the toxicity of methotrexateSulfamerazine	The sulfamide increases the toxicity of methotrexateSulfamethazine	The sulfamide increases the toxicity of methotrexateSulfamethizole	The sulfamide increases the toxicity of methotrexateSulfamethoxazole	The sulfamide increases the toxicity of methotrexateSulfapyridine	The sulfamide increases the toxicity of methotrexateSulfathiazole	The sulfamide increases the toxicity of methotrexateSulfisoxazole	The sulfamide increases the toxicity of methotrexateSulfadimethoxine	The sulfamide increases the toxicity of methotrexate 
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    CYP450  Drug Interaction | 
    
      [CYP450 TableÁ÷Á¢Á¶È¸] 
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    | Food Interaction | 
    
       Methotrexate¿¡ ´ëÇÑ Food Interaction Á¤º¸ Take without regard to meals. Limit caffeine intake.Milk appears to reduce its absorption. 
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    | Drug Target | 
    
      
      [Drug Target]
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    | Description | 
    
       Methotrexate¿¡ ´ëÇÑ Description Á¤º¸ 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] 
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    | Dosage Form | 
    
       Methotrexate¿¡ ´ëÇÑ Dosage_Form Á¤º¸ Solution	IntramuscularSolution	IntrathecalSolution	IntravenousTablet	Oral 
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    | Drug Category | 
    
       Methotrexate¿¡ ´ëÇÑ Drug_Category Á¤º¸ Abortifacient AgentsAbortifacient Agents, NonsteroidalAntimetabolitesAntimetabolites, AntineoplasticAntineoplastic AgentsAntirheumatic AgentsDermatologic AgentsEnzyme InhibitorsFolic Acid AntagonistsImmunosuppressive AgentsNucleic Acid Synthesis Inhibitors 
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    | Smiles String Canonical | 
    
       Methotrexate¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ CN(CC1=CN=C2N=C(N)N=C(N)C2=N1)C1=CC=C(C=C1)C(=O)NC(CCC(O)=O)C(O)=O 
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    | Smiles String Isomeric | 
    
       Methotrexate¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ CN(CC1=CN=C2N=C(N)N=C(N)C2=N1)C1=CC=C(C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O 
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    | InChI Identifier | 
    
       Methotrexate¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C20H22N8O5/c1-28(9-11-8-23-17-15(24-11)16(21)26-20(22)27-17)12-4-2-10(3-5-12)18(31)25-13(19(32)33)6-7-14(29)30/h2-5,8,13H,6-7,9H2,1H3,(H,25,31)(H,29,30)(H,32,33)(H4,21,22,23,26,27)/t13-/m0/s1/f/h25,29,32H,21-22H2 
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    | Chemical IUPAC Name | 
    
       Methotrexate¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ (2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methylamino]benzoyl]amino]pentanedioic acid 
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    | Drug-Induced Toxicity Related Proteins | 
    
      METHOTREXATE ÀÇ Drug-Induced Toxicity Related ProteinÁ¤º¸ Replated Protein:Thymidine kinase Drug:methotrexate Toxicity:apoptotic cell death and epidermal hyperplasia.  [¹Ù·Î°¡±â] Replated Protein:Pulmonary surfactant-associated protein D  Drug:methotrexate Toxicity:lung injury.  [¹Ù·Î°¡±â] Replated Protein:Glutamate oxaloacetate transaminase Drug:methotrexate Toxicity:increase in the death rate.  [¹Ù·Î°¡±â] Replated Protein:Cellular tumor antigen p53  Drug:Methotrexate  Toxicity:induce apoptotic cell death.  [¹Ù·Î°¡±â] METHOTREXATE (MTX) ÀÇ Drug-Induced Toxicity Related ProteinÁ¤º¸ Replated Protein:Uracil-DNA glycosylase  Drug:methotrexate (MTX) Toxicity:MTX-induced genotoxic damage.  [¹Ù·Î°¡±â] 
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