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Identification
Name Amphotericin B
Accession Number DB00681 (APRD00797)
Type small molecule
Groups approved
Description

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.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • AMPH-B
  • Amphortericin B
  • Amphotericine B
  • Liposomal Amphotericin B
Synonyms
AMPH-B
Amphortericin B
Amphotericine B
Liposomal Amphotericin B
Salts Not Available
Brand names
Name Company
Abelcet
ABLC
AmBisome
Ampho-Moronal
Amphocin
Amphotec
Amphotericin
Amphozone
Fungilin
Fungisone
Fungizone
Fungizone Intravenous
Halizon
HSDB 3008 IAB
LNS-AmB
Mysteclin-F
SinuNase
Tegopen
First Prev Next Last
Brand mixtures Not Available
Categories
  • Anti-Bacterial Agents
  • Antifungal Agents
  • Antiprotozoal Agents
  • Amebicides
CAS number 1397-89-3
Weight Average: 924.079
Monoisotopic: 923.487849915
Chemical Formula C47H73NO17
InChI Key InChIKey=APKFDSVGJQXUKY-INPOYWNPSA-N
InChI
InChI=1S/C47H73NO17/c1-27-17-15-13-11-9-7-5-6-8-10-12-14-16-18-34(64-46-44(58)41(48)43(57)30(4)63-46)24-38-40(45(59)60)37(54)26-47(61,65-38)25-33(51)22-36(53)35(52)20-19-31(49)21-32(50)23-39(55)62-29(3)28(2)42(27)56/h5-18,27-38,40-44,46,49-54,56-58,61H,19-26,48H2,1-4H3,(H,59,60)/b6-5+,9-7+,10-8+,13-11+,14-12+,17-15+,18-16+/t27-,28-,29-,30+,31+,32+,33-,34-,35+,36+,37-,38-,40+,41-,42+,43+,44-,46-,47+/m0/s1
Plain Text
IUPAC Name
(1R,3S,5R,6R,9R,11R,15S,16R,17R,18S,19E,21E,23E,25E,27E,29E,31E,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
SMILES
C[C@H]1O[C@@H](O[C@@H]2C[C@@H]3O[C@@](O)(C[C@H](O)[C@H]3C(O)=O)C[C@@H](O)C[C@@H](O)[C@H](O)CC[C@@H](O)C[C@@H](O)CC(=O)O[C@@H](C)[C@H](C)[C@H](O)[C@@H](C)\C=C\C=C\C=C\C=C\C=C\C=C\C=C\2)[C@@H](O)[C@@H](N)[C@@H]1O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
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
Pharmacology
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
Pharmacoeconomics
Manufacturers
  • Apothecon inc div bristol myers squibb
  • Sigma tau pharmaceuticals inc
  • Three rivers pharmaceuticals llc
  • Astellas pharma us inc
  • Abbott laboratories
  • Abraxis pharmaceutical products
  • Teva parenteral medicines inc
  • X gen pharmaceuticals inc
  • Bristol myers squibb co
Packagers
Dosage forms
Form Route Strength
Powder, for solution Intravenous
Powder, for suspension Intravenous
Suspension Intravenous
Prices
Unit description Cost Unit
Ambisome 50 mg vial 188.4 USD vial
Amphotec 100 mg vial 160.0 USD vial
Amphotec 50 mg vial 93.33 USD vial
Fungizone Iv 50 mg/vial 72.5 USD vial
Amphotericin b powder 29.99 USD g
Amphotericin b 50 mg vial 24.5 USD vial
Abelcet 5 mg/ml vial p-f 12.0 USD ml
Patents
Country Patent Number Approved Expires (estimated)
United States 5965156 1996-10-12 2016-10-12
United States 5874104 1996-02-23 2016-02-23
Canada 1339008 1997-03-25 2014-03-25
Canada 1336890 1995-09-05 2012-09-05
Properties
State solid
Melting point 170.0 oC
Experimental Properties
Property Value Source
water solubility 750 mg/L PhysProp
logP 0.8 PhysProp
Predicted Properties
Property Value Source
water solubility 8.19e-02 g/l ALOGPS
logP -0.66 ALOGPS
logP -2.3 ChemAxon Molconvert
logS -4 ALOGPS
pKa 11.83 ChemAxon Molconvert
hydrogen acceptor count 17 ChemAxon Molconvert
hydrogen donor count 12 ChemAxon Molconvert
polar surface area 319.61 ChemAxon Molconvert
rotatable bond count 3 ChemAxon Molconvert
refractivity 244.67 ChemAxon Molconvert
polarizability 99.45 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00203 Link_out
KEGG Compound C06573 Link_out
PubChem Compound 5280965 Link_out
PubChem Substance 46505473 Link_out
ChemSpider 14245 Link_out
Therapeutic Targets Database DAP001322 Link_out
PharmGKB PA448415 Link_out
Drug Product Database 29149 Link_out
RxList http://www.rxlist.com/cgi/generic2/amphoter.htm Link_out
Drugs.com http://www.drugs.com/cdi/amphotericin-b.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Amphotericin_B Link_out
ATC Codes
  • A01AB04
  • A07AA07
  • G01AA03
  • J02AA01
AHFS Codes
  • 08:14.28
PDB Entries Not Available
FDA label show (1.02 MB)
MSDS show (73.1 KB)
Interactions
Drug Interactions
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
Food Interactions Not Available
Targets

1. Ergosterol, Candida albicans

Pharmacological action: yes
Actions: binder

References:
  1. Laniado-Laborin R, Cabrales-Vargas MN: Amphotericin B: side effects and toxicity. Rev Iberoam Micol. 2009 Dec 31;26(4):223-7. Pubmed
  2. Baginski M, Czub J: Amphotericin B and its new derivatives – mode of action. Curr Drug Metab. 2009 Jun;10(5):459-69. Pubmed
  3. Baginski M, Sternal K, Czub J, Borowski E: Molecular modelling of membrane activity of amphotericin B, a polyene macrolide antifungal antibiotic. Acta Biochim Pol. 2005;52(3):655-8. Epub 2005 Aug 5. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 14, 2012 11:43