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药品详细

Anagrelide(阿那格雷)

化学结构式图
中文名
阿那格雷
英文名
Anagrelide
分子式
C10H7Cl2N3O
化学名
6,7-dichloro-1H,2H,3H,5H-imidazolidino[2,1-b]quinazolin-2-one
分子量
Average: 256.088
Monoisotopic: 254.996617275
CAS号
68475-42-3
ATC分类
L01X 其它抗肿瘤药
药物类型
small molecule
阶段
approved
商品名
Agrylin;Xagrid;
同义名
Anagrelide HCL;Anagrelide Hydrochloride;BL-4162A;
基本介绍

Anagrelide is a drug used for the treatment of essential thrombocytosis (ET; essential thrombocythemia). It also has been used in the treatment of chronic myeloid leukemia. [Wikipedia]

生产厂家
  • Alphapharm pty ltd
  • Barr laboratories inc
  • Impax laboratories inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mylan laboratories inc
  • Roxane laboratories inc
  • Sandoz inc
  • Shire development inc
  • Watson laboratories
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Voglova J, Maisnar V, Beranek M, Chrobak L: [Combination of imatinib and anagrelide in treatment of chronic myeloid leukemia in blastic phase] Vnitr Lek. 2006 Sep;52(9):819-22. Pubmed
  2. Petrides PE: Anagrelide: what was new in 2004 and 2005? Semin Thromb Hemost. 2006 Jun;32(4 Pt 2):399-408. Pubmed
  3. Harrison CN, Campbell PJ, Buck G, Wheatley K, East CL, Bareford D, Wilkins BS, van der Walt JD, Reilly JT, Grigg AP, Revell P, Woodcock BE, Green AR: Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med. 2005 Jul 7;353(1):33-45. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes Not Available
Substructures Not Available
适应症
Cancer 癌症;
药理
Indication For the treatment of patients with thrombocythemia, secondary to myeloproliferative disorders, to reduce the elevated platelet count and the risk of thrombosis and to ameliorate associated symptoms including thrombo-hemorrhagic events.
Pharmacodynamics Anagrelide is a drug used for the treatment of essential thrombocytosis (ET; essential thrombocythemia). It works by inhibiting the maturation of megakaryocytes into platelets. The exact mechanism of action is unclear, although it is known to be a potent (IC50 = 36nM) inhibitor of phosphodiesterase-III.
Mechanism of action The mechanism by which anagrelide reduces blood platelet count is still under investigation. Studies in patients support a hypothesis of dose-related reduction in platelet production resulting from a decrease in megakaryocyte hypermaturation. In blood withdrawn from normal volunteers treated with anagrelide, a disruption was found in the postmitotic phase of megakaryocyte development and a reduction in megakaryocyte size and ploidy. At therapeutic doses, anagrelide does not produce significant changes in white cell counts or coagulation parameters, and may have a small, but clinically insignificant effect on red cell parameters. Anagrelide inhibits cyclic AMP phosphodiesterase III (PDEIII). PDEIII inhibitors can also inhibit platelet aggregation. However, significant inhibition of platelet aggregation is observed only at doses of anagrelide higher than those required to reduce platelet count.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism
Extensive, with < 1% recovered unchanged in the urine. Metabolized primarily in the liver by cytochrome P450 1A2 (CYP1A2). Recently, it was found that anagrelide is bio-transformed in humans into two major metabolites (6,7-dichloro-3-hydroxy-1,5 dihydro-imidazo[2,1-b]quinazolin-2-one (BCH24426) and 2-amino-5,6-dichloro-3,4,-dihydroquinazoline (RL603). Whether these metabolites have biological activities that may underlie the mode of action of the parent drug is presently unclear.

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

Substrate Enzymes Product
Anagrelide
    		2-amino-5,6-dichloro-3,4,-dihydroquinazoline Details
    Anagrelide
      		6,7-dichloro-3-hydroxy-1,5 dihydro-imidazo[2,1-b]quinazolin-2-one Details
      Route of elimination Not Available
      Half life At fasting and at a dose of 0.5 mg of anagrelide, the plasma half-life is 1.3 hours.
      Clearance Not Available
      Toxicity There are no reports of overdosage with anagrelide, however thrombocytopenia, which can potentially cause bleeding, is expected from overdosage. Single oral doses of anagrelide at 2,500, 1,500 and 200 mg/kg in mice, rats and monkeys, respectively, were not lethal. Symptoms of acute toxicity were: decreased motor activity in mice and rats and softened stools and decreased appetite in monkeys.
      Affected organisms
      • Humans and other mammals
      Pathways Not Available
      理化性质
      Properties
      State solid
      Experimental Properties
      Property Value Source
      melting point 280 °C Not Available
      water solubility Very slightly soluble Not Available
      logP 2.4 Not Available
      Predicted Properties
      Property Value Source
      water solubility 2.79e-01 g/l ALOGPS
      logP 1.95 ALOGPS
      logP 1.94 ChemAxon
      logS -3 ALOGPS
      pKa (strongest acidic) 12.55 ChemAxon
      pKa (strongest basic) 3.62 ChemAxon
      physiological charge 0 ChemAxon
      hydrogen acceptor count 3 ChemAxon
      hydrogen donor count 1 ChemAxon
      polar surface area 44.7 ChemAxon
      rotatable bond count 0 ChemAxon
      refractivity 63.25 ChemAxon
      polarizability 23.61 ChemAxon
      药物相互作用
      Drug Interaction
      Ginkgo biloba Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
      Treprostinil The prostacyclin analogue, Treprostinil, increases the risk of bleeding when combined with the antiplatelet agent, Anagrelide. Monitor for increased bleeding during concomitant thearpy.
      食物相互作用
      • Food appears to reduce the area under the curve by 13.8%, without clinical consequence.
      • Take without regard to meals.

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