Identification

Summary

Amphotericin B is an antifungal used to treat fungal infections in neutropenic patients, cryptococcal meningitis in HIV infection, fungal infections, and leishmaniasis.

Brand Names
Abelcet, Ambisome, Amphotec, Fungizone
Generic Name
Amphotericin B
DrugBank Accession Number
DB00681
Background

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.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 924.079
Monoisotopic: 923.487849915
Chemical Formula
C47H73NO17
Synonyms
  • Amfotericina B
  • AMPH-b
  • Amphotericin B
  • Amphotéricine B
  • Amphotericinum B
  • Liposomal amphotericin B
External IDs
  • NSC-527017
  • RP 17774

Pharmacology

Indication

Used to treat potentially life threatening fungal infections.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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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.

TargetActionsOrganism
AErgosterol
binder
Candida albicans
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]
Adverse Effects
Adverseeffects
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Toxicity

Oral, rat: LD50 = >5 gm/kg. Amphotericin B overdoses can result in cardio-respiratory arrest.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirAmphotericin B may decrease the excretion rate of Abacavir which could result in a higher serum level.
AcebutololThe risk or severity of adverse effects can be increased when Amphotericin B is combined with Acebutolol.
AceclofenacThe risk or severity of nephrotoxicity can be increased when Amphotericin B is combined with Aceclofenac.
AcemetacinThe risk or severity of nephrotoxicity can be increased when Amphotericin B is combined with Acemetacin.
AcenocoumarolThe therapeutic efficacy of Acenocoumarol can be increased when used in combination with Amphotericin B.
AcetaminophenAmphotericin B may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
AcetazolamideThe therapeutic efficacy of Acetazolamide can be decreased when used in combination with Amphotericin B.
AcetyldigitoxinThe risk or severity of adverse effects can be increased when Amphotericin B is combined with Acetyldigitoxin.
Acetylsalicylic acidThe risk or severity of nephrotoxicity can be increased when Amphotericin B is combined with Acetylsalicylic acid.
AcipimoxThe risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Amphotericin B is combined with Acipimox.
Interactions
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Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Amphotericin B Cholesteryl Sulfate Complex774X4698X3120895-52-5Not applicable
CorifunginL26BTK479141610-51-9MTSXPVSZJVNPBE-ALEYTFIZSA-M
International/Other Brands
Abelect (Cephalon) / Ampho-Moronal (Dermapharm) / Amphocil (Alza) / Amphocin (Pfizer) / Amphotericin (Bristol-Myers Squibb) / Fungilin (Sigma) / Fungisome / Fungizone Intravenous (Bristol-Myers Squibb) / Halizon (Fuji Yakuhin)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AbelcetSuspension5 mg / mLIntravenousLeadiant Biosciences, Inc1997-09-25Not applicableCanada flag
AmBisomeInjection, powder, lyophilized, for solution50 mg/12.5mLIntravenousAstellas Pharma US, Inc.1997-08-11Not applicableUS flag
AmBisomePowder, for solution50 mg / vialIntravenousAstellas Pharma Inc2000-05-29Not applicableCanada flag
AmphotecInjection, lipid complex50 mg/10mLIntravenousInterMune, Inc.2006-02-27Not applicableUS flag
AmphotecInjection, lipid complex100 mg/100mgIntravenousKadmon Pharmaceuticals2005-05-202011-05-31US flag
AmphotecInjection, lipid complex100 mg/20mLIntravenousInterMune, Inc.2006-02-27Not applicableUS flag
AmphotecInjection, lipid complex50 mg/50mgIntravenousKadmon Pharmaceuticals2005-05-202011-05-31US flag
Amphotec 100 mgPowder, for suspension100 mg / vialIntravenousThree Rivers Pharmaceuticals Llc2004-06-172013-08-22Canada flag
Amphotec 50 mgPowder, for suspension50 mg / vialIntravenousThree Rivers Pharmaceuticals Llc2007-02-262013-08-22Canada flag
Amphotericin B for Injection, USPPowder, for solution50 mg / vialIntravenousSterimax IncNot applicableNot applicableCanada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Amphotericin BInjection, powder, lyophilized, for solution50 mg/10mLIntravenousX-GEN Pharmaceuticals, Inc.1992-04-29Not applicableUS flag
FungizoneInjection, powder, lyophilized, for solution50 mg/10mLIntravenousE.R. Squibb & Sons, L.L.C.1966-03-012005-09-30US flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
AbelcetAmphotericin B (5 mg/1mL) + DL-dimyristoylphosphatidylcholine (3.4 mg/1mL) + DL-dimyristoylphosphatidylglycerol (1.5 mg/1mL)InjectionIntravenousLeadiant Biosciences, Inc.2010-10-18Not applicableUS flag

Categories

ATC Codes
G01AA03 — Amphotericin bA07AA07 — Amphotericin bA01AB04 — Amphotericin bJ02AA01 — Amphotericin b
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as aminoglycosides. These are molecules or a portion of a molecule composed of amino-modified sugars.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbohydrates and carbohydrate conjugates
Direct Parent
Aminoglycosides
Alternative Parents
Macrolides and analogues / Hexoses / O-glycosyl compounds / Beta hydroxy acids and derivatives / Oxanes / Dicarboxylic acids and derivatives / Secondary alcohols / 1,2-aminoalcohols / Amino acids / Lactones
show 11 more
Substituents
1,2-aminoalcohol / Acetal / Alcohol / Aliphatic heteropolycyclic compound / Amine / Amino acid / Amino acid or derivatives / Aminoglycoside core / Beta-hydroxy acid / Carbonyl group
show 24 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
antibiotic antifungal drug, macrolide antibiotic, polyene antibiotic (CHEBI:2682) / Plyenes (C06573) / Polyenes (LMPK06000002)
Affected organisms
  • Various Fungus Species

Chemical Identifiers

UNII
7XU7A7DROE
CAS number
1397-89-3
InChI Key
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[C@H](C)[C@@H](O)[C@H](N)[C@@H]3O)\C=C\C=C\C=C\C=C\C=C\C=C\C=C\[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]1C(O)=O)O2

References

Synthesis Reference

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

US4035567
General References
Not Available
Human Metabolome Database
HMDB0014819
KEGG Drug
D00203
KEGG Compound
C06573
PubChem Compound
5280965
PubChem Substance
46505473
ChemSpider
10237579
BindingDB
50457967
RxNav
236594
ChEBI
2682
ChEMBL
CHEMBL267345
ZINC
ZINC000253387843
Therapeutic Targets Database
DAP001322
PharmGKB
PA448415
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Amphotericin_B
FDA label
Download (1.02 MB)
MSDS
Download (73.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedOtherObesity, Morbid1
4CompletedPreventionCandidiasis1
4CompletedPreventionLeukemias1
4CompletedTreatmentCandidemia / Candidiasis, Invasive1
4CompletedTreatmentCentral Line Fungal Infections1
4CompletedTreatmentFungus, Nail / Infections, Fungal / Onychomycosis1
4CompletedTreatmentInfections, Fungal / Liver Diseases1
4CompletedTreatmentInvasive Aspergillosis1
4CompletedTreatmentPost Kala Azar Dermal Leishmaniasis1
4CompletedTreatmentVisceral Leishmaniasis1

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
  • Astellas Pharma Inc.
  • Ben Venue Laboratories Inc.
  • Bristol-Myers Squibb Co.
  • Cardinal Health
  • DSM Corp.
  • E.R. Squibb and Sons LLC
  • Enzon Inc.
  • Gilead Sciences Inc.
  • Medisca Inc.
  • Oso Biopharmaceuticals Manufacturing LLC
  • Pharmacia Inc.
  • Sigma-Tau Pharmaceuticals Inc.
  • Teva Pharmaceutical Industries Ltd.
  • Three Rivers Pharmaceuticals LLC
  • X-Gen Pharmaceuticals
Dosage Forms
FormRouteStrength
InjectionIntravenous
SuspensionIntravenous5 mg / mL
Injection, suspensionIntravenous
Injection, solution, concentrateIntravenous5 MG/ML
Injection, powder, lyophilized, for solutionIntravenous50 mg/12.5mL
Powder, for solutionIntravenous50 mg / vial
Injection, powder, for solutionParenteral
Injection, powder, for suspensionIntravenous
Injection, powder, for solutionIntravenous50 mg
PowderIntravenous
LozengeOral
TabletOral
SuspensionOral
Powder, for solution
Solution50 mg/1vial
SuspensionIntravenous100 mg
SuspensionIntravenous50 mg
Injection, powder, for solutionIntravenous
Injection, lipid complexIntravenous100 mg/100mg
Injection, lipid complexIntravenous100 mg/20mL
Injection, lipid complexIntravenous50 mg/10mL
Injection, lipid complexIntravenous50 mg/50mg
Powder, for suspensionIntravenous100 mg / vial
Powder, for suspensionIntravenous50 mg / vial
Injection, powder, lyophilized, for solutionIntravenous
OintmentOphthalmic
Injection, powder, lyophilized, for solutionIntravenous50 mg/10mL
Powder, for solutionParenteral50 MG
InjectionIntravenous
Injection, powder, lyophilized, for solutionIntravenous50 mg
PowderIntravenous50 mg
Injection, powder, for suspensionIntravenous50 mg
CreamVaginal
PowderIntravenous50 mg/1vial
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)Region
CA1339008No1997-03-252014-03-25Canada flag
CA1336890No1995-09-052012-09-05Canada flag
US6406713No2002-06-182019-06-18US flag
US5874104No1999-02-232016-02-23US flag
US5965156No1999-10-122016-10-12US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)170.0 °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 FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Drugtargets2
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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. [Article]
  2. Baginski M, Czub J: Amphotericin B and its new derivatives - mode of action. Curr Drug Metab. 2009 Jun;10(5):459-69. [Article]
  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. [Article]

Drug created at June 13, 2005 13:24 / Updated at October 26, 2021 21:40