用户名： 密   码：
注册 | 忘记密码？
药品详细

Azathioprine(硫唑嘌呤)

化学结构式图
中文名
硫唑嘌呤
英文名
Azathioprine
分子式
C9H7N7O2S
化学名
6-[(1-methyl-4-nitro-1H-imidazol-5-yl)sulfanyl]-7H-purine
分子量
Average: 277.263
Monoisotopic: 277.038193193
CAS号
446-86-6
ATC分类
L04A 未知
药物类型
small molecule
阶段
approved
商品名
Azamun;Azanin;Azasan;Ccucol;Imuran;Imurek;Imurel;Muran;
同义名
Azathioprin;Azathioprine Sodium;Azatioprin;Azothioprine;
基本介绍

An immunosuppressive pro-drug. It is converted into 6-mercaptopurine in the body where it blocks purine metabolism and DNA synthesis.

生产厂家
  • Aaipharma llc
  • Bedford laboratories div ben venue laboratories inc
  • Mylan pharmaceuticals inc
  • Prometheus laboratories inc
  • Roxane laboratories inc
  • Zydus pharmaceuticals usa inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Konstantopoulou M, Belgi A, Griffiths KD, Seale JR, Macfarlane AW: Azathioprine-induced pancytopenia in a patient with pompholyx and deficiency of erythrocyte thiopurine methyltransferase. BMJ. 2005 Feb 12;330(7487):350-1. Pubmed
  2. Woodroffe R, Yao GL, Meads C, Bayliss S, Ready A, Raftery J, Taylor RS: Clinical and cost-effectiveness of newer immunosuppressive regimens in renal transplantation: a systematic review and modelling study. Health Technol Assess. 2005 May;9(21):1-179, iii-iv. Pubmed
  3. Gombar VK, Enslein K, Blake BW: Carcinogenicity of azathioprine: an S-AR investigation. Mutat Res. 1993 May;302(1):7-12. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Nitroimidazoles
  • Purines and Purine Derivatives
Substructures
  • Nitroimidazoles
  • Ethers
  • Oxoazaniums
  • Nitro compounds
  • Pyrimidines and Derivatives
  • Imidazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Purines and Purine Derivatives
  • Cyanamides
适应症
IMMUNOSUPPRESSIVE 免疫抑制;
药理
Indication For use in rheumatoid arthritis, preventing renal transplant rejection, Crohn's disease, and colitis.
Pharmacodynamics 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.
Mechanism of action 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.
Absorption Well absorbed following oral administration.
Volume of distribution Not Available
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. 6-mercaptopurine is subsequently metabolized primarily by xanthine oxidase.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Azathioprine
S-methylazathioprine Details
Azathioprine
    		6-Thioguanine Details
    Azathioprine
      		6-Mercaptopurine Details
      Azathioprine
        		6-Thioinosine 5'-monophosphate Details
        Azathioprine
          		6-thioguanylic acid Details
          Azathioprine
            		6-thioinosine triphosphate Details
            Azathioprine
              		6-thioinosinic acid Details
              Azathioprine
                		6-thioxanthylic acid Details
                Azathioprine
                  		8-hydroxythioguanine Details
                  Azathioprine
                    		Thio-deoxyguanosine triphosphate Details
                    Azathioprine
                      		Thioguanine diphosphate Details
                      Azathioprine
                        		Thioguanine triphosphate Details
                        Azathioprine
                          		6-thiouric acid Details
                          Azathioprine
                            		6-Thioxanthine 5'-monophosphate Details
                            Route of elimination Not Available
                            Half life Approximately 5 hours for the unchanged drug and its metabolites.
                            Clearance Not Available
                            Toxicity 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.
                            Affected organisms
                            • Humans and other mammals
                            Pathways
                            Pathway Name SMPDB ID
                            Smp00427 Azathioprine Pathway SMP00427
                            理化性质
                            Properties
                            State solid
                            Experimental Properties
                            Property Value Source
                            melting point 243.5 °C PhysProp
                            water solubility 272 mg/L Not Available
                            logP 0.10 HANSCH,C ET AL. (1995)
                            pKa 7.87 (at 25 °C) MITRA,AK & NARURKAR,MM (1986)
                            Predicted Properties
                            Property Value Source
                            water solubility 1.07e+00 g/l ALOGPS
                            logP 0.84 ALOGPS
                            logP 1.17 ChemAxon
                            logS -2.4 ALOGPS
                            pKa (strongest acidic) 8.65 ChemAxon
                            pKa (strongest basic) 4 ChemAxon
                            physiological charge 0 ChemAxon
                            hydrogen acceptor count 6 ChemAxon
                            hydrogen donor count 1 ChemAxon
                            polar surface area 118.1 ChemAxon
                            rotatable bond count 3 ChemAxon
                            refractivity 70.95 ChemAxon
                            polarizability 24.26 ChemAxon
                            药物相互作用
                            Drug Interaction
                            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.
                            Dicumarol 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.
                            食物相互作用
                            • Take with food to reduce irritation.

                            返回 | 收藏