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Identification
NameAmphotericin B
Accession NumberDB00681  (APRD00797)
TypeSmall Molecule
GroupsApproved, Investigational
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
Synonyms
Amfotericina B
AMPH-b
Amphotericin B
Amphotéricine B
Amphotericinum B
C-AmB
Liposomal amphotericin b
External Identifiers
  • RP 17774
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Abelcetsuspension5 mgintravenousSigma Tau Pharmaceuticals Inc1997-09-25Not applicableCanada
Ambisomeinjection, powder, lyophilized, for solution50 mg/12.5mLintravenousAstellas Pharma US, Inc.1997-08-11Not applicableUs
Ambisomepowder for solution50 mgintravenousAstellas Pharma Canada Inc2000-05-29Not applicableCanada
Amphotecinjection, lipid complex100 mg/100mgintravenousKadmon Pharmaceuticals LLC2005-05-202015-12-29Us
Amphotecinjection, lipid complex50 mg/50mgintravenousKadmon Pharmaceuticals LLC2005-05-202015-12-29Us
Amphotec 100 mgpowder for suspension100 mgintravenousThree Rivers Pharmaceuticals Llc2004-06-172013-08-22Canada
Amphotec 50 mgpowder for suspension50 mgintravenousThree Rivers Pharmaceuticals Llc2007-02-262013-08-22Canada
Amphotericin B for Injection, USPpowder for solution50 mgintravenousSterimax IncNot applicableNot applicableCanada
Fungizone Intravenous Injection 50mgpowder for solution50 mgintravenousBristol Myers Squibb Canada1958-12-31Not applicableCanada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Amphotericin Binjection, powder, lyophilized, for solution50 mg/10mLintravenousX Gen Pharmaceuticals, Inc.1992-04-29Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AbelectCephalon
Ampho-MoronalDermapharm
AmphocilAlza
AmphocinPfizer
AmphotericinBristol-Myers Squibb
FungilinSigma
FungisomeNot Available
FungizoneBristol-Myers Squibb
Fungizone IntravenousBristol-Myers Squibb
HalizonFuji Yakuhin
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Amphotericin B Cholesteryl Sulfate Complex
ThumbNot applicableDBSALT000993
Categories
UNII7XU7A7DROE
CAS number1397-89-3
WeightAverage: 924.079
Monoisotopic: 923.487849915
Chemical FormulaC47H73NO17
InChI KeyInChIKey=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
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
[H][C@]12C[C@@H](O[C@@H]3O[[email protected]](C)[C@@H](O)[[email protected]](N)[C@@H]3O)\C=C\C=C\C=C\C=C\C=C\C=C\C=C\[[email protected]](C)[C@@H](O)[C@@H](C)[[email protected]](C)OC(=O)C[[email protected]](O)C[[email protected]](O)CC[C@@H](O)[[email protected]](O)C[[email protected]](O)C[C@](O)(C[[email protected]](O)[[email protected]]1C(O)=O)O2
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as macrolides and analogues. These are organic compounds containing a lactone ring of at least twelve members.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassMacrolides and analogues
Sub ClassNot Available
Direct ParentMacrolides and analogues
Alternative Parents
Substituents
  • Macrolide
  • Glucosamine
  • Amino sugar
  • O-glycosyl compound
  • Glycosyl compound
  • Amino saccharide
  • Beta-hydroxy acid
  • Oxane
  • Monosaccharide
  • Hydroxy acid
  • Dicarboxylic acid or derivatives
  • Secondary alcohol
  • Polyol
  • Lactone
  • Hemiacetal
  • Carboxylic acid ester
  • 1,2-diol
  • 1,2-aminoalcohol
  • Oxacycle
  • Organoheterocyclic compound
  • Carboxylic acid
  • Carboxylic acid derivative
  • Acetal
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Carbonyl group
  • Amine
  • Alcohol
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationUsed to treat potentially life threatening fungal infections.
PharmacodynamicsAmphotericin 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 actionAmphotericin 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.
Related Articles
AbsorptionBioavailability is 100% for intravenous infusion.
Volume of distributionNot Available
Protein bindingHighly bound (>90%) to plasma proteins.
Metabolism

Exclusively renal

Route of eliminationNot Available
Half lifeAn 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]
ToxicityOral, rat: LD50 = >5 gm/kg. Amphotericin B overdoses can result in cardio-respiratory arrest.
Affected organisms
  • Various Fungus Species
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9308
Blood Brain Barrier-0.9659
Caco-2 permeable-0.7539
P-glycoprotein substrateSubstrate0.6404
P-glycoprotein inhibitor INon-inhibitor0.7322
P-glycoprotein inhibitor IINon-inhibitor0.5977
Renal organic cation transporterNon-inhibitor0.9491
CYP450 2C9 substrateNon-substrate0.7992
CYP450 2D6 substrateNon-substrate0.8785
CYP450 3A4 substrateSubstrate0.5496
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.941
CYP450 2D6 inhibitorNon-inhibitor0.9444
CYP450 2C19 inhibitorNon-inhibitor0.921
CYP450 3A4 inhibitorNon-inhibitor0.9381
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.984
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.9682
BiodegradationNot ready biodegradable0.9414
Rat acute toxicity2.2357 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9777
hERG inhibition (predictor II)Non-inhibitor0.7887
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
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
FormRouteStrength
Suspensionintravenous5 mg
Injection, powder, lyophilized, for solutionintravenous50 mg/12.5mL
Powder for solutionintravenous50 mg
Injection, lipid complexintravenous100 mg/100mg
Injection, lipid complexintravenous50 mg/50mg
Powder for suspensionintravenous100 mg
Powder for suspensionintravenous50 mg
Injection, powder, lyophilized, for solutionintravenous50 mg/10mL
Prices
Unit descriptionCostUnit
Ambisome 50 mg vial188.4USD vial
Amphotec 100 mg vial160.0USD vial
Amphotec 50 mg vial93.33USD vial
Fungizone Iv 50 mg/vial72.5USD vial
Amphotericin b powder29.99USD g
Amphotericin b 50 mg vial24.5USD vial
Abelcet 5 mg/ml vial p-f12.0USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA1336890 No1995-09-052012-09-05Canada
CA1339008 No1997-03-252014-03-25Canada
US5874104 No1996-02-232016-02-23Us
US5965156 No1996-10-122016-10-12Us
US6406713 No1999-06-182019-06-18Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point170.0 °CNot Available
water solubility750 mg/L (at 28 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP0.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0819 mg/mLALOGPS
logP-0.66ALOGPS
logP-2.3ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)3.58ChemAxon
pKa (Strongest Basic)9.11ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count17ChemAxon
Hydrogen Donor Count12ChemAxon
Polar Surface Area319.61 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity244.67 m3·mol-1ChemAxon
Polarizability99.45 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Frank Sipos, “Process for producing the methyl ester of amphotericin B.” U.S. Patent US4035567, issued March, 1976.

US4035567
General ReferencesNot Available
External Links
ATC CodesA01AB04A07AA07G01AA03J02AA01
AHFS Codes
  • 08:14.28
PDB EntriesNot Available
FDA labelDownload (1.02 MB)
MSDSDownload (73.1 KB)
Interactions
Drug Interactions
Drug
AmikacinAmphotericin B may increase the nephrotoxic activities of Amikacin.
ArbekacinAmphotericin B may increase the nephrotoxic activities of Arbekacin.
BetamethasoneBetamethasone may increase the hypokalemic activities of Amphotericin B.
BudesonideBudesonide may increase the hypokalemic activities of Amphotericin B.
ColistimethateAmphotericin B may increase the nephrotoxic activities of Colistimethate.
ColistinAmphotericin B may increase the nephrotoxic activities of Colistin.
CorticotropinCorticotropin may increase the hypokalemic activities of Amphotericin B.
Cortisone acetateCortisone acetate may increase the hypokalemic activities of Amphotericin B.
CyclosporineAmphotericin B may increase the nephrotoxic activities of Cyclosporine.
DexamethasoneDexamethasone may increase the hypokalemic activities of Amphotericin B.
DigoxinThe risk or severity of adverse effects can be increased when Amphotericin B is combined with Digoxin.
FluconazoleThe therapeutic efficacy of Amphotericin B can be decreased when used in combination with Fluconazole.
FlucytosineThe risk or severity of adverse effects can be increased when Amphotericin B is combined with Flucytosine.
FludrocortisoneFludrocortisone may increase the hypokalemic activities of Amphotericin B.
FlunisolideFlunisolide may increase the hypokalemic activities of Amphotericin B.
FoscarnetFoscarnet may increase the nephrotoxic activities of Amphotericin B.
FramycetinAmphotericin B may increase the nephrotoxic activities of Framycetin.
GentamicinAmphotericin B may increase the nephrotoxic activities of Gentamicin.
HydrocortisoneHydrocortisone may increase the hypokalemic activities of Amphotericin B.
IsavuconazoniumThe therapeutic efficacy of Amphotericin B can be decreased when used in combination with Isavuconazonium.
ItraconazoleThe therapeutic efficacy of Amphotericin B can be decreased when used in combination with Itraconazole.
KanamycinAmphotericin B may increase the nephrotoxic activities of Kanamycin.
KetoconazoleThe therapeutic efficacy of Amphotericin B can be decreased when used in combination with Ketoconazole.
MethylprednisoloneMethylprednisolone may increase the hypokalemic activities of Amphotericin B.
MometasoneMometasone may increase the hypokalemic activities of Amphotericin B.
NeomycinAmphotericin B may increase the nephrotoxic activities of Neomycin.
NetilmicinAmphotericin B may increase the nephrotoxic activities of Netilmicin.
PosaconazoleThe therapeutic efficacy of Amphotericin B can be decreased when used in combination with Posaconazole.
PrednisolonePrednisolone may increase the hypokalemic activities of Amphotericin B.
PrednisonePrednisone may increase the hypokalemic activities of Amphotericin B.
Repository corticotropinRepository corticotropin may increase the hypokalemic activities of Amphotericin B.
RibostamycinAmphotericin B may increase the nephrotoxic activities of Ribostamycin.
SpectinomycinAmphotericin B may increase the nephrotoxic activities of Spectinomycin.
StreptomycinAmphotericin B may increase the nephrotoxic activities of Streptomycin.
TobramycinAmphotericin B may increase the nephrotoxic activities of Tobramycin.
TriamcinoloneTriamcinolone may increase the hypokalemic activities of Amphotericin B.
VoriconazoleThe therapeutic efficacy of Amphotericin B can be decreased when used in combination with Voriconazole.
Food InteractionsNot Available

Targets

1. Ergosterol
Kind
Small molecule
Organism
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. doi: 10.1016/j.riam.2009.06.003. [PubMed:19836985 ]
  2. Baginski M, Czub J: Amphotericin B and its new derivatives - mode of action. Curr Drug Metab. 2009 Jun;10(5):459-69. [PubMed:19689243 ]
  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:16086075 ]
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Drug created on June 13, 2005 07:24 / Updated on June 27, 2016 01:53