Tìm theo
Methotrexate
Các tên gọi khác (13 ) :
  • 4-amino-10-methylfolic acid
  • 4-amino-N(10)-Methylpteroylglutamic acid
  • Amethopterin
  • Emtexate
  • Ledertrexate
  • Methotrexat
  • Méthotrexate
  • Methotrexatum
  • Metotrexato
  • MTX
  • N-[4-[[(2,4-Diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamic acid
  • Rheumatrex
  • Trexall
Thuốc chống ung thư và tác động vào hệ thống miễn dịch
Thuốc Gốc
Small Molecule
CAS: 59-05-2
ATC: L01BA01, L04AX03
ĐG : Apotheca Inc.
CTHH: C20H22N8O5
PTK: 454.4393
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]
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C20H22N8O5
Phân tử khối
454.4393
Monoisotopic mass
454.171315854
InChI
InChI=1S/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
InChI Key
InChIKey=FBOZXECLQNJBKD-ZDUSSCGKSA-N
IUPAC Name
(2S)-2-[(4-{[(2,4-diaminopteridin-6-yl)methyl](methyl)amino}phenyl)formamido]pentanedioic acid
Traditional IUPAC Name
methotrexate
SMILES
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
Độ tan chảy
195 °C
Độ hòa tan
2600 mg/L
logP
-1.85
logS
-3.4
pKa (strongest acidic)
3.41
pKa (Strongest Basic)
2.81
PSA
210.54 Å2
Refractivity
119.21 m3·mol-1
Polarizability
44.54 Å3
Rotatable Bond Count
9
H Bond Acceptor Count
12
H Bond Donor Count
5
Physiological Charge
-2
Number of Rings
3
Bioavailability
0
Ghose Filter
true
MDDR-Like Rule
true
caco2 Permeability
-5.92
pKa
4.7
Dược Lực Học : 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.
Cơ Chế Tác Dụng : 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] 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.
Dược Động Học :
▧ Absorption :
Oral absorption is dose dependent in adults and leukemic pediatric patients. In adults, peak serum levels are reached within one to two hours. At doses of 30 mg/m^2 or less, methotrexate is generally well absorbed with a mean bioavailability of 60%. At doses greater than 80 mg/m^2, the absorption of the doses is significantly less due to a saturation effect.
▧ Volume of Distribution :
* 0.18 L/kg [initial volume of distribution (Vd)] * 0.4 - 0.8 L/kg [steady state Vd] Methotrexate competes with reduced folates for active transport across cell membranes by means of a single carrier-mediated active transport process. At serum concentrations greater than 100 micromolar, passive diffusion becomes a major pathway by which effective intracellular concentrations can be achieved. Methotrexate does not cross the blood-brain-barrier.
▧ Protein binding :
50% bound to protein, primarily to albumin
▧ Metabolism :
Methotrexate undergoes hepatic and intracellular metabolism to polyglutamated forms which can be converted back to methotrexate by hydroxylase enzymes. These polyglutamates act as inhibitors of dihydrofolate reductase and thymidylate synthetase. A small amount of metabolism to 7-hydroxymethotrexate may occur at doses commonly prescribed. Furthermore, intestinal flora partially metabolizes methotrexate after oral administration.
▧ Route of Elimination :
Renal excretion is the primary route of elimination and is dependent upon dosage and route of administration. 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 (less than 30 mg/m^2): 3 to 10 hours; High doses: 8 to 15 hours.
▧ Clearance :
Methotrexate clearance rates vary widely and are generally decreased at higher doses. Delayed drug clearance has been identified as one of the major factors responsible for methotrexate toxicity.
Độc Tính : Symptoms of overdose include bone marrow suppression and gastrointestinal toxicity. LD50=43mg/kg(orally in rat).
Chỉ Định : Methotrexate is indicated in the treatment of gestational choriocarcinoma, chorioadenoma destruens and hydatidiform mole. In acute lymphocytic leukemia, methotrexate is indicated in the prophylaxis of meningeal leukemia and is used in maintenance therapy in combination with other chemotherapeutic agents. Methotrexate is also indicated in the treatment of meningeal leukemia. Methotrexate is used alone or in combination with other anticancer agents in the treatment of breast cancer, epidermoid cancers of the head and neck, advanced mycosis fungoides (cutaneous T cell lymphoma), and lung cancer, particularly squamous cell and small cell types. Methotrexate is also used in combination with other chemotherapeutic agents in the treatment of advanced stage non-Hodgkin’s lymphomas. Methotrexate is indicated in the symptomatic control of severe, recalcitrant, disabling psoriasis. Methotrexate is indicated in the management of selected adults with severe, active rheumatoid arthritis (ACR criteria), or children with active polyarticular-course juvenile rheumatoid arthritis.
Tương Tác Thuốc :
  • 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
  • Benzylpenicillin 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.
  • Eltrombopag Increases levels of Methotrexate via metabolism decrease. OATP transporter protein inhibition.
  • 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 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
  • Rilonacept Rilonacept and methotrexate both increase immunosuppressive effects; combination may increase risk of myelosuppression.
  • 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.
Liều Lượng & Cách Dùng : Injection, powder, lyophilized, for solution - Parenteral - 1 g
Injection, solution - Parenteral - 25 mg/mL; 50 mg/2 mL; 100 mg/4 mL; 200 mg/8 mL; 250 mg/10 mL; 1 g/40 mL
Tablet - Oral - 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty : Teva
    Sản phẩm biệt dược : Abitrexate
  • Công ty : Naprod
    Sản phẩm biệt dược : Alltrex
  • Công ty : TRB
    Sản phẩm biệt dược : Artrait
  • Công ty : Schering-Plough
    Sản phẩm biệt dược : Atrexel
  • Công ty : Bendalis
    Sản phẩm biệt dược : Bendatrexat
  • Công ty : Cadila
    Sản phẩm biệt dược : Carditrex
  • Công ty : East West
    Sản phẩm biệt dược : Dermotrex
  • Công ty : Ebewe
    Sản phẩm biệt dược : Ebetrex
  • Công ty :
    Sản phẩm biệt dược : Emtexate
  • Công ty : Biodim
    Sản phẩm biệt dược : Ledertrexate
  • Công ty : Pfizer
    Sản phẩm biệt dược : Maxtrex
  • Công ty : Hospira
    Sản phẩm biệt dược : Meisusheng
  • Công ty : Cadila HC
    Sản phẩm biệt dược : Mexate
  • Công ty :
    Sản phẩm biệt dược : Otrexup
  • Công ty : Wyeth KK
    Sản phẩm biệt dược : Rheumatrex
  • Công ty : Barr
    Sản phẩm biệt dược : Trexall
  • Công ty : Atafarm
    Sản phẩm biệt dược : Trexan
  • Công ty : Dabur Pharma
    Sản phẩm biệt dược : Zexate
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00563
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=126941
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46507678
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C01937
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00142
ChemSpider
http://www.chemspider.com/Chemical-Structure.112728.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=18050
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/67253-320-10
PharmGKB
http://www.pharmgkb.org/drug/PA450428
Wikipedia
http://en.wikipedia.org/wiki/Methotrexate
RxList
http://www.rxlist.com/cgi/generic/mtx.htm
PDRhealth
http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/met1257.shtml
Drugs.com
http://www.drugs.com/methotrexate.html
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