Tìm theo
Azathioprine
Các tên gọi khác (3) :
  • 6-((1-Methyl-4-nitro-1H-imidazol-5-yl)thio)-1H-purine
  • 6-(1'-Methyl-4'-nitro-5'-imidazolyl)-mercaptopurine
  • Imuran (tn)
antirheumatic agents, immunosuppressive agents, antimetabolites, antimetabolites antineoplastic
Thuốc Gốc
Small Molecule
CAS: 446-86-6
ATC: L04AX01
ĐG : AAIPharma Inc. , http://www.aaipharma.com
CTHH: C9H7N7O2S
PTK: 277.263
An immunosuppressive antimetabolite pro-drug. It is an imidazolyl derivative of 6-mercaptopurine and many of its biological effects are similar to those of the parent compound. Azathioprine is converted into 6-mercaptopurine in the body where it blocks purine metabolism and DNA synthesis.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C9H7N7O2S
Phân tử khối
277.263
Monoisotopic mass
277.038193193
InChI
InChI=1S/C9H7N7O2S/c1-15-4-14-7(16(17)18)9(15)19-8-5-6(11-2-10-5)12-3-13-8/h2-4H,1H3,(H,10,11,12,13)
InChI Key
InChIKey=LMEKQMALGUDUQG-UHFFFAOYSA-N
IUPAC Name
6-[(1-methyl-4-nitro-1H-imidazol-5-yl)sulfanyl]-7H-purine
Traditional IUPAC Name
azathioprine
SMILES
CN1C=NC(=C1SC1=NC=NC2=C1NC=N2)[N+]([O-])=O
Độ tan chảy
243.5 °C
Độ hòa tan
Insoluble
logP
0.10
logS
-2.4
pKa (strongest acidic)
8.65
pKa (Strongest Basic)
4
PSA
118.1 Å2
Refractivity
70.95 m3·mol-1
Polarizability
24.26 Å3
Rotatable Bond Count
3
H Bond Acceptor Count
6
H Bond Donor Count
1
Physiological Charge
0
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
pKa
7.87 (at 25 °C)
Dược Lực Học : Azathioprine is a chemotherapy drug, now rarely used for chemotherapy but more for immunosuppression in organ transplantation and autoimmune disease such as rheumatoid arthritis or inflammatory bowel disease or Crohn's disease. It is a pro-drug, converted in the body to the active metabolite 6-mercaptopurine. Azathioprine acts to inhibit purine synthesis necessary for the proliferation of cells, especially leukocytes and lymphocytes. It is a safe and effective drug used alone in certain autoimmune diseases, or in combination with other immunosuppressants in organ transplantation. Its most severe side effect is bone marrow suppression, and it should not be given in conjunction with purine analogues such as allopurinol. The enzyme thiopurine S-methyltransferase (TPMT) deactivates 6-mercaptopurine. Genetic polymorphisms of TPMT can lead to excessive drug toxicity, thus assay of serum TPMT may be useful to prevent this complication.
Cơ Chế Tác Dụng : An immunosuppressive antimetabolite pro-drug. It is an imidazolyl derivative of 6-mercaptopurine and many of its biological effects are similar to those of the parent compound. Azathioprine is converted into 6-mercaptopurine in the body where it blocks purine metabolism and DNA synthesis. Azathioprine antagonizes purine metabolism and may inhibit synthesis of DNA, RNA, and proteins. It may also interfere with cellular metabolism and inhibit mitosis. Its mechanism of action is likely due to incorporation of thiopurine analogues into the DNA structure, causing chain termination and cytotoxicity.
Dược Động Học :
▧ Absorption :
Well absorbed following oral administration.
▧ Protein binding :
Azathioprine and the metabolite mercaptopurine are moderately bound to serum proteins (30%).
▧ Metabolism :
Primarily converted to the active metabolites 6-mercaptopurine and 6-thioinosinic acid via a non-enzymatica process and glutathione transferases. Activation of 6-mercaptopurine occurs via hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and a series of multi-enzymatic processes involving kinases to form 6-thioguanine nucleotides (6-TGNs) as major metabolites
▧ Route of Elimination :
Both compounds are rapidly eliminated from blood and are oxidized or methylated in erythrocytes and liver; no azathioprine or mercaptopurine is detectable in urine after 8 hours.
Độc Tính : The oral LD50 for single doses of azathioprine in mice and rats are 2500 mg/kg and 400 mg/kg, respectively. Very large doses of this antimetabolite may lead to marrow hypoplasia, bleeding, infection, and death.
Chỉ Định : For use in rheumatoid arthritis, preventing renal transplant rejection, Crohn's disease, and colitis.
Tương Tác Thuốc :
  • Acenocoumarol Azathioprine may decrease the anticoagulant effect of acenocoumarol.
  • Allopurinol Allopurinol may increase the effect of thiopurine, azathioprine.
  • Aminosalicylic Acid Aminosalicylic acid may increase the toxicity of thiopurine, azathioprine.
  • Anisindione Azathioprine may decrease the anticoagulant effect of anisindione.
  • Atracurium The agent decreases the effect of the muscle relaxant
  • Canakinumab results in increased immunosuppressive effects; increases the risk of infection.
  • Dicoumarol Azathioprine may decrease the anticoagulant effect of dicumarol.
  • Doxacurium chloride The agent decreases the effect of the muscle relaxant
  • Febuxostat Coadministration of febuxostat with xanthine oxidase substrate drugs (azathioprine, mercaptopurine or theophylline) could increase plasma concentrations of these drugs, since these drugs are metabolized by xanthine oxidase, resulting in severe toxicity; hence their concomitant use is contraindicated. Since febuxostat does not inhibit or induce cytochrome P450 enzymes it lacks significant drug interactions with other drugs metabolized of these enzymes.
  • Mesalazine Mesalazine may increase the toxicity of thiopurine, azathioprine.
  • Metocurine The agent decreases the effect of the muscle relaxant
  • Mivacurium The agent decreases the effect of the muscle relaxant
  • Olsalazine Olsalazine may increase the toxicity of thiopurine, azathioprine.
  • Pancuronium The agent decreases the effect of the muscle relaxant
  • Rilonacept results in increased immunosuppressive effects; increases the risk of infection.
  • Sulfasalazine Sulfasalazine may increase the toxicity of thiopurine, azathioprine.
  • Trandolapril Trandolapril may increase the risk of neutropenia. Monitor for increased toxic effects of Azathioprine if Trandolapril is initiated or dose increased.
  • Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
  • Tubocurarine The agent decreases the effect of the muscle relaxant
  • Vecuronium The agent decreases the effect of the muscle relaxant
  • Warfarin Azathioprine may decrease the anticoagulant effect of warfarin.
Liều Lượng & Cách Dùng : Injection, powder, for solution - Intravenous - 100 mg
Tablet - Oral - 50 mg, 75 mg, 100 mg
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00993
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=2265
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46508252
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C06837
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00238
ChemSpider
http://www.chemspider.com/Chemical-Structure.2178.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0378-1005-01
PharmGKB
http://www.pharmgkb.org/drug/PA448515
Wikipedia
http://en.wikipedia.org/wiki/Azathioprine
RxList
http://www.rxlist.com/cgi/generic/azathioprine.htm
Drugs.com
http://www.drugs.com/cdi/azathioprine.html
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