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药品详细

Nitazoxanide(硝唑尼特)

化学结构式图
中文名
硝唑尼特
英文名
Nitazoxanide
分子式
C12H9N3O5S
化学名
2-[(5-nitro-1,3-thiazol-2-yl)carbamoyl]phenyl acetate
分子量
Average: 307.282
Monoisotopic: 307.026291103
CAS号
55981-09-4
ATC分类
P01A 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

Nitazoxanide, also known by the brand name Alinia, is a synthetic nitrothiazolyl-salicylamide derivative and an anti-protozoal agent. It is approved for treatment of infectious diarrhea caused by Cryptosporidium parvum and Giardia lamblia in patients 1 year of age and older. Following oral administration it is rapidly hydrolyzed to its active metabolite, tizoxanide, which is 99% protein bound. Peak concentrations are observed 1–4 hours after administration. It is excreted in the urine, bile and feces. Untoward effects include abdominal pain, vomiting and diarrhea. [Wikipedia]

生产厂家
  • Romark laboratories
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Parasitic infections. Am J Transplant. 2004 Nov;4 Suppl 10:142-55. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Phenylacetates
  • Benzamides
Substructures
  • Carboxylic Acids and Derivatives
  • Acetates
  • Oxoazaniums
  • Phenols and Derivatives
  • Amino Ketones
  • Phenylacetates
  • Ethers
  • Benzene and Derivatives
  • Nitro compounds
  • Thiazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Carboxamides and Derivatives
  • Benzoyl Derivatives
  • Phenyl Esters
  • Benzamides
适应症
药理
Indication For the treatment of diarrhea in adults and children caused by the protozoa Giardia lamblia and for the treatment of diarrhea in children caused by the protozoa Cryptosporidium parvum.
Pharmacodynamics Nitazoxanide is an antifolate containing the pyrrolopyrimidine-based nucleus that exerts its antineoplastic activity by disrupting folate-dependent metabolic processes essential for cell replication. In vitro studies have shown that nitazoxanide inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), all folate-dependent enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides. Nitazoxanide is transported into cells by both the reduced folate carrier and membrane folate binding protein transport systems. Once in the cell, nitazoxanide is converted to polyglutamate forms by the enzyme folylpolyglutamate synthetase. The polyglutamate forms are retained in cells and are inhibitors of TS and GARFT. Polyglutamation is a time- and concentration-dependent process that occurs in tumor cells and, to a lesser extent, in normal tissues. Polyglutamated metabolites have an increased intracellular half-life resulting in prolonged drug action in malignant cells.
Mechanism of action The antiprotozoal activity of nitazoxanide is believed to be due to interference with the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme-dependent electron transfer reaction which is essential to anaerobic energy metabolism. Studies have shown that the PFOR enzyme from Giardia lamblia directly reduces nitazoxanide by transfer of electrons in the absence of ferredoxin. The DNA-derived PFOR protein sequence of Cryptosporidium parvum appears to be similar to that of Giardia lamblia. Interference with the PFOR enzyme-dependent electron transfer reaction may not be the only pathway by which nitazoxanide exhibits antiprotozoal activity.
Absorption The relative bioavailability of the suspension compared to the tablet was 70%. When administered with food the AUC and Cmax increased by two-fold and 50%, respectively, for the tablet and 45 to 50% and ≤ 10%, respectively, for the oral suspension.
Volume of distribution Not Available
Protein binding Very High (greater than 99%), bound to proteins. Binding is not affected by degree of renal impairment.
Metabolism
Rapidly hydrolyzed to an active metabolite, tizoxanide (desacetyl-nitazoxanide), followed by conjugation, primarily by glucuronidation to tizoxanide glucuronide.

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

Substrate Enzymes Product
Nitazoxanide
    		Desacetyl-nitazoxanide Details
    Nitazoxanide
      		Tizoxanide glucuronide Details
      Route of elimination Tizoxanide is excreted in the urine, bile and feces, and tizoxanide glucuronide is excreted in urine and bile. Approximately two-thirds of the oral dose of nitazoxanide is excreted in the feces and one-third in the urine.
      Half life 3.5 hours in patients with normal renal function
      Clearance Not Available
      Toxicity In acute studies in rodents and dogs, the oral LD50 was higher than 10,000 mg/kg. Single oral doses of up to 4000 mg nitazoxanide have been administered to healthy adult volunteers without significant adverse effects.
      Affected organisms
      • Protozoa
      Pathways Not Available
      理化性质
      Properties
      State solid
      Experimental Properties
      Property Value Source
      melting point 202 °C Not Available
      logP 1.2 Not Available
      Predicted Properties
      Property Value Source
      water solubility 7.55e-03 g/l ALOGPS
      logP 2.14 ALOGPS
      logP 2.12 ChemAxon
      logS -4.6 ALOGPS
      pKa (strongest acidic) 8.3 ChemAxon
      pKa (strongest basic) -4.2 ChemAxon
      physiological charge 0 ChemAxon
      hydrogen acceptor count 5 ChemAxon
      hydrogen donor count 1 ChemAxon
      polar surface area 114.11 ChemAxon
      rotatable bond count 5 ChemAxon
      refractivity 73.89 ChemAxon
      polarizability 27.54 ChemAxon
      药物相互作用
      食物相互作用
      Not Available

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