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药品详细

Amphotericin B(两性霉素B)

化学结构式图
中文名
两性霉素B
英文名
Amphotericin B
分子式
C47H73NO17
化学名
(1R,3S,5R,6R,9R,11R,15S,16R,17R,18S,33R,35S,36R,37S)-33-{[(2R,3S,4S,5S,6R)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy}-1,3,5,6,9,11,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,23,25,27,29,31-heptaene-36-carboxylic acid
分子量
Average: 924.079
Monoisotopic: 923.487849915
CAS号
1397-89-3
ATC分类
A01A 未知;A07A 未知;G01A 未知;J02A Antimycotics for Systemic Use
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

Amphotericin B shows a high order of in vitro activity against many species of fungi. Histoplasma capsulatum, Coccidioides immitis, Candida species, Blastomyces dermatitidis, Rhodotorula, Cryptococcus neoformans, Sporothrix schenckii, Mucor mucedo, and Aspergillus fumigatus are all inhibited by concentrations of amphotericin B ranging from 0.03 to 1.0 mcg/mL in vitro. While Candida albicans is generally quite susceptible to amphotericin B, non-albicans species may be less susceptible. Pseudallescheria boydii and Fusarium sp. are often resistant to amphotericin B. The antibiotic is without effect on bacteria, rickettsiae, and viruses.

生产厂家
  • Abbott laboratories
  • Abraxis pharmaceutical products
  • Apothecon inc div bristol myers squibb
  • Astellas pharma us inc
  • Bristol myers squibb co
  • Sigma tau pharmaceuticals inc
  • Teva parenteral medicines inc
  • Three rivers pharmaceuticals llc
  • X gen pharmaceuticals inc
封装厂家
参考
Synthesis Reference Not Available
General Reference Not Available
剂型
规格
化合物类型
Type small molecule
Classes
  • Aminoglycosides
Substructures
  • Carboxylic Acids and Derivatives
  • Aminoglycosides
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Pyrans
  • Acetates
  • Acetals and Derivatives
  • Lactones
  • Aliphatic and Aryl Amines
  • Ethers
  • Amino Alcohols
  • Alcohols and Polyols
  • Heterocyclic compounds
适应症
药理
Indication Used to treat potentially life threatening fungal infections.
Pharmacodynamics Amphotericin B shows a high order of in vitro activity against many species of fungi. Histoplasma capsulatum, Coccidioides immitis, Candida species, Blastomyces dermatitidis, Rhodotorula, Cryptococcus neoformans, Sporothrix schenckii, Mucor mucedo, and Aspergillus fumigatus are all inhibited by concentrations of amphotericin B ranging from 0.03 to 1.0 mcg/mL in vitro. While Candida albicans is generally quite susceptible to amphotericin B, non-albicans species may be less susceptible. Pseudallescheria boydii and Fusarium sp. are often resistant to amphotericin B. The antibiotic is without effect on bacteria, rickettsiae, and viruses.
Mechanism of action Amphotericin B is fungistatic or fungicidal depending on the concentration obtained in body fluids and the susceptibility of the fungus. The drug acts by binding to sterols (ergosterol) in the cell membrane of susceptible fungi. This creates a transmembrane channel, and the resultant change in membrane permeability allowing leakage of intracellular components. Ergosterol, the principal sterol in the fungal cytoplasmic membrane, is the target site of action of amphotericin B and the azoles. Amphotericin B, a polyene, binds irreversibly to ergosterol, resulting in disruption of membrane integrity and ultimately cell death.
Absorption Bioavailability is 100% for intravenous infusion.
Volume of distribution Not Available
Protein binding Highly bound (>90%) to plasma proteins.
Metabolism
Exclusively renal
Route of elimination Not Available
Half life An elimination half-life of approximately 15 days follows an initial plasma half-life of about 24 hours.
Clearance
  • 39 +/- 22 mL/hr/kg [febrile neutropenic cancer and bone marrow transplant patients receiving infusion of 1 mg/kg/day at Day 1]
  • 17 +/- 6 mL/hr/kg [febrile neutropenic cancer and bone marrow transplant patients receiving infusion of 1 mg/kg/day 3-20 days later]
  • 51 +/- 44 mL/hr/kg [febrile neutropenic cancer and bone marrow transplant patients receiving infusion of 2.5 mg/kg/day at Day 1]
  • 22 +/- 15 mL/hr/kg [febrile neutropenic cancer and bone marrow transplant patients receiving infusion of 2.5 mg/kg/day 3-20 days later]
  • 21 +/- 14 mL/hr/kg [febrile neutropenic cancer and bone marrow transplant patients receiving infusion of 5 mg/kg/day at Day 1]
  • 11 +/- 6 mL/hr/kg [febrile neutropenic cancer and bone marrow transplant patients receiving infusion of 5 mg/kg/day 3-20 days later]
Toxicity Oral, rat: LD50 = >5 gm/kg. Amphotericin B overdoses can result in cardio-respiratory arrest.
Affected organisms
  • Various Fungus Species
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
melting point 170.0 °C Not Available
water solubility 750 mg/L (at 28 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP 0.8 Not Available
Predicted Properties
Property Value Source
water solubility 8.19e-02 g/l ALOGPS
logP -0.66 ALOGPS
logP -2.3 ChemAxon
logS -4 ALOGPS
pKa (strongest acidic) 3.58 ChemAxon
pKa (strongest basic) 9.11 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 17 ChemAxon
hydrogen donor count 12 ChemAxon
polar surface area 319.61 ChemAxon
rotatable bond count 3 ChemAxon
refractivity 244.67 ChemAxon
polarizability 99.45 ChemAxon
药物相互作用
Drug Interaction
Colistimethate Amphotericin B may enhance the nephrotoxic effect of Colistimethate. Due to the potential for additive or synergistic nephrotoxicity between colistimethate and other nephrotoxic drugs, such as amphotericin B, this combination should be avoided whenever possible. If these agents must be used together, patients' renal function should be monitored closely.
Cyclosporine Monitor for nephrotoxicity
Tacrolimus Additive renal impairment may occur during concomitant therapy with Amphotericin B. Use caution during concomitant therapy.
Tobramycin Increased risk of nephrotoxicity
食物相互作用
Not Available

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