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药品详细

Pyrimethamine(乙胺嘧啶)

化学结构式图
中文名
乙胺嘧啶
英文名
Pyrimethamine
分子式
C12H13ClN4
化学名
5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine
分子量
Average: 248.711
Monoisotopic: 248.082874143
CAS号
58-14-0
ATC分类
P01B 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

One of the folic acid antagonists that is used as an antimalarial or with a sulfonamide to treat toxoplasmosis. [PubChem]

生产厂家
  • Glaxosmithkline llc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Gatton ML, Martin LB, Cheng Q: Evolution of resistance to sulfadoxine-pyrimethamine in Plasmodium falciparum. Antimicrob Agents Chemother. 2004 Jun;48(6):2116-23. Pubmed
  2. Sirichaiwat C, Intaraudom C, Kamchonwongpaisan S, Vanichtanankul J, Thebtaranonth Y, Yuthavong Y: Target guided synthesis of 5-benzyl-2,4-diamonopyrimidines: their antimalarial activities and binding affinities to wild type and mutant dihydrofolate reductases from Plasmodium falciparum. J Med Chem. 2004 Jan 15;47(2):345-54. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Phenylpropenes
Substructures
  • Phenylpropenes
  • Aliphatic and Aryl Amines
  • Benzene and Derivatives
  • Aryl Halides
  • Halobenzenes
  • Pyrimidines and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Imines
  • Cyanamides
适应症
药理
Indication For the treatment of toxoplasmosis and acute malaria; For the prevention of malaria in areas non-resistant to pyrimethamine
Pharmacodynamics Pyrimethamine is an antiparasitic compound commonly used as an adjunct in the treatment of uncomplicated, chloroquine resistant, P. falciparum malaria. Pyrimethamine is a folic acid antagonist and the rationale for its therapeutic action is based on the differential requirement between host and parasite for nucleic acid precursors involved in growth. This activity is highly selective against plasmodia and Toxoplasma gondii. Pyrimethamine possesses blood schizonticidal and some tissue schizonticidal activity against malaria parasites of humans. However, the 4-amino-quinoline compounds are more effective against the erythrocytic schizonts. It does not destroy gametocytes, but arrests sporogony in the mosquito. The action of pyrimethamine against Toxoplasma gondii is greatly enhanced when used in conjunction with sulfonamides.
Mechanism of action Pyrimethamine inhibits the dihydrofolate reductase of plasmodia and thereby blocks the biosynthesis of purines and pyrimidines, which are essential for DNA synthesis and cell multiplication. This leads to failure of nuclear division at the time of schizont formation in erythrocytes and liver.
Absorption Well absorbed with peak levels occurring between 2 to 6 hours following administration
Volume of distribution Not Available
Protein binding 87%
Metabolism
Hepatic
Route of elimination Not Available
Half life 96 hours
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Plasmodium
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
melting point 233.5 °C PhysProp
water solubility 121 mg/L Not Available
logP 2.69 HANSCH,C ET AL. (1995)
pKa 7.34 (at 20 °C) PERRIN,DD (1972)
Predicted Properties
Property Value Source
water solubility 1.79e-01 g/l ALOGPS
logP 2.62 ALOGPS
logP 2.75 ChemAxon
logS -3.1 ALOGPS
pKa (strongest acidic) 17.22 ChemAxon
pKa (strongest basic) 7.77 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 77.82 ChemAxon
rotatable bond count 2 ChemAxon
refractivity 71.54 ChemAxon
polarizability 25.79 ChemAxon
药物相互作用
Drug Interaction
Artemether Pyrimethamine may increase the adverse effects of artemether. Combination therapy is contraindicated unless there are no other treatment options.
Lumefantrine Pyrimethamine may increase the adverse effects of lumefantrine. Combination therapy is contraindicated unless there are no other treatment options.
Tamoxifen Pyrimethamine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
Tamsulosin Pyrimethamine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Pyrimethamine is initiated, discontinued, or dose changed.
Tramadol Pyrimethamine may decrease the effect of Tramadol by decreasing active metabolite production.
食物相互作用
  • Folic acid needs increased.
  • Take with food to reduce irritation.

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