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药品详细

Amifostine(阿米福汀)

化学结构式图
中文名
阿米福汀
英文名
Amifostine
分子式
C5H15N2O3PS
化学名
({2-[(3-aminopropyl)amino]ethyl}sulfanyl)phosphonic acid
分子量
Average: 214.223
Monoisotopic: 214.054099558
CAS号
20537-88-6
ATC分类
V03A 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

A phosphorothioate proposed as a radiation-protective agent. It causes splenic vasodilation and may block autonomic ganglia. [PubChem]

生产厂家
  • Medimmune
  • Sun pharma global inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Santini V, Giles FJ: The potential of amifostine: from cytoprotectant to therapeutic agent. Haematologica. 1999 Nov;84(11):1035-42. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Phosphonic Acids and Derivatives
Substructures
  • Hydroxy Compounds
  • Phosphonic Acids and Derivatives
  • Aliphatic and Aryl Amines
  • Phosphinic Acids and Derivatives
适应症
药理
Indication For reduction in the cumulative renal toxicity in patients with ovarian cancer (using cisplatin) and moderate to severe xerostomia in patients undergoing post-operative radiation treatment for head and neck cancer.
Pharmacodynamics Amifostine is an organic thiophosphate cytoprotective agent indicated to reduce the cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer or non-small cell lung cancer and also to reduce the incidence of moderate to severe xerostomia in patients undergoing post-operative radiation treatment for head and neck cancer. Amifostine is a prodrug that is dephosphorylated by alkaline phosphatase in tissues to a pharmacologically active free thiol metabolite, believed to be responsible for the reduction of the cumulative renal toxicity of cisplatin and for the reduction of the toxic effects of radiation on normal oral tissues. Healthy cells are preferentially protected because amifostine and metabolites are present in healthy cells at 100-fold greater concentrations than in tumour cells.
Mechanism of action The thiol metabolite is responsible for most of the cytoprotective and radioprotective properties of amifostine. It is readily taken up by cells where it binds to and detoxifies reactive metabolites of platinum and alkylating agents as well as scavenges free radicals. Other possible effects include inhibition of apoptosis, alteration of gene expression and modification of enzyme activity.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism
Amifostine is rapidly dephosphorylated by alkaline phosphatase in tissues primarily to the active free thiol metabolite and, subsequently, to a less active disulfide metabolite.
Route of elimination After a 10-second bolus dose of 150 mg/m2 of ETHYOL, renal excretion of the parent drug and its two metabolites was low during the hour following drug administration, averaging 0.69%, 2.64% and 2.22% of the administered dose for the parent, thiol and disulfide, respectively.
Half life 8 minutes
Clearance Not Available
Toxicity Rat LD50: 826 mg/kg
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
water solubility 1000 mg/mL Not Available
logP -1.9 Not Available
Predicted Properties
Property Value Source
water solubility 1.87e+01 g/l ALOGPS
logP -1.4 ALOGPS
logP -3.7 ChemAxon
logS -1.1 ALOGPS
pKa (strongest acidic) 2.06 ChemAxon
pKa (strongest basic) 11.01 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 5 ChemAxon
hydrogen donor count 4 ChemAxon
polar surface area 95.58 ChemAxon
rotatable bond count 7 ChemAxon
refractivity 51.28 ChemAxon
polarizability 21.01 ChemAxon
药物相互作用
Drug Interaction
Azilsartan medoxomil Azilsartan medoxomil used in combintation with amifostine may lead to hypotension.
Chlorothiazide Antihypertensives may enhance the hypotensive effect of amifostine. When amifostine is used at doses recommended for chemotherapy, antihypertensive medications should be withheld for 24 hours prior to amifostine administration to avoid excessive hypotension during or immediately after infusion. If antihypertensive therapy can not be withheld, then that patient should not receive amifostine. Caution is recommended when using amifostine at the lower doses recommended for radiotherapy, but routine interruption of antihypertensive therapy is not recommended in these patients.
Telmisartan Telmisartan may increase the hypotensive effect of Amifostine. At chemotherapeutic doses of Amifostine, Telmisartan should be withheld for 24 hours prior to Amifostine administration. Use caution at lower doses of Amifostine.
Terazosin Terazosin may increase the hypotensive effect of Amifostine. At chemotherapeutic doses of Amifostine, Terazosin should be withheld for 24 hours prior to Amifostine administration. Use caution at lower doses of Amifostine.
Tolazamide Additive hypotensive effects may occur. At chemotherapeutic doses of Amifostine, Tolazamide should be withheld for 24 hours prior to Amifostine administration. Use caution at lower doses of Amifostine.
Torasemide Torasemide may increase the hypotensive effect of Amifostine. At chemotherapeutic doses of Amifostine, Torasemide should be withheld for 24 hours prior to Amifostine administration. Use caution at lower doses of Amifostine.
Trandolapril Trandolapril may increase the hypotensive effect of Amifostine. At chemotherapeutic doses of Amifostine, Trandolapril should be withheld for 24 hours prior to Amifostine administration. Use caution at lower doses of Amifostine.
Trichlormethiazide Trichlormethiazide may increase the hypotensive effect of Amifostine. At chemotherapeutic doses of Amifostine, Trichlomethiazide should be withheld for 24 hours prior to Amifostine administration. Use caution at lower doses of Amifostine.
Valsartan Additive hypotensive effects may occur. At chemotherapeutic doses of Amifostine, Valsartan should be withheld for 24 hours prior to Amifostine administration. Use caution at lower doses of Amifostine.
Verapamil Verapamil may enhance the hypotensive effect of Amifostine. At chemotherapeutic doses of Amifostine, Verapamil should be withheld for 24 hours prior to Amifostine administration. Caution should be used at lower Amifostine doses used during radiotherapy, but routine interruption of Verapamil therapy is not recommended.
食物相互作用
Not Available

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