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6) °ñ¼ö¿¡ ÀÌ»ó¹ÝÀÀÀ» ³ªÅ¸³»´Â ¾à¹° : °ñ¼ö¿¡ ÀÌ»ó¹ÝÀÀÀ» ³ªÅ¸³»´Â ¾à¹°·Î ¾à¹°Ä¡·á(¿¹ : ¼³Æù¾Æ¹Ìµå, Æ®¸®¸ÞÅäÇÁ¸²-¼³ÆÄ¸ÞÅä»çÁ¹, Ŭ·Î¶÷Æä´ÏÄÝ, ÇǸ®¸ÞŸ¹Î)¸¦ ÇÒ °æ¿ì ½É°¢ÇÑ Á¶Ç÷ Àå¾Ö°¡ ³ªÅ¸³¯ ¼ö ÀÖÀ¸¹Ç·Î ÁÖÀǸ¦ ±â¿ï¿©¾ß ÇÑ´Ù.
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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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| SNP Á¤º¸ |
Name:Methotrexate (DB00563)
Interacting Gene/Enzyme:Canalicular multispecific organic anion transporter 1 (Gene symbol = ABCC2) Swissprot Q92887
SNP(s):ABCC2 IVS 23+56 (T allele)
Effect:General toxicity (gastrointestinal and hepatotoxicity)
Reference(s):Ranganathan P, Culverhouse R, Marsh S, Mody A, Scott-Horton TJ, Brasington R, Joseph A, Reddy V, Eisen S, McLeod HL: Methotrexate (MTX) pathway gene polymorphisms and their effects on MTX toxicity in Caucasian and African American patients with rheumatoid arthritis. J Rheumatol. 2008 Apr;35(4):572-9. Epub 2008 Mar 15. [PubMed]
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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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