Amphotericin B

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

Similar Structures

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.

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Associated Conditions

Contraindications & Blackbox Warnings

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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.

Target	Actions	Organism
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

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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.

Drug	Interaction
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Abacavir	Amphotericin B may decrease the excretion rate of Abacavir which could result in a higher serum level.
Acebutolol	The risk or severity of adverse effects can be increased when Amphotericin B is combined with Acebutolol.
Aceclofenac	The risk or severity of nephrotoxicity can be increased when Amphotericin B is combined with Aceclofenac.
Acemetacin	The risk or severity of nephrotoxicity can be increased when Amphotericin B is combined with Acemetacin.
Acenocoumarol	The therapeutic efficacy of Acenocoumarol can be increased when used in combination with Amphotericin B.
Acetaminophen	Amphotericin B may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
Acetazolamide	The therapeutic efficacy of Acetazolamide can be decreased when used in combination with Amphotericin B.
Acetyldigitoxin	The risk or severity of adverse effects can be increased when Amphotericin B is combined with Acetyldigitoxin.
Acetylsalicylic acid	The risk or severity of nephrotoxicity can be increased when Amphotericin B is combined with Acetylsalicylic acid.
Acipimox	The risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Amphotericin B is combined with Acipimox.

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Food Interactions

No interactions found.

Products

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Product Ingredients

Ingredient	UNII	CAS	InChI Key
Amphotericin B Cholesteryl Sulfate Complex	774X4698X3	120895-52-5	Not applicable
Corifungin	L26BTK4791	41610-51-9	MTSXPVSZJVNPBE-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

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Abelcet	Suspension	5 mg / mL	Intravenous	Leadiant Biosciences, Inc	1997-09-25	Not applicable
AmBisome	Powder, for solution	50 mg / vial	Intravenous	Astellas Pharma Inc	2000-05-29	Not applicable
AmBisome	Injection, powder, lyophilized, for solution	50 mg/12.5mL	Intravenous	Astellas Pharma US, Inc.	1997-08-11	Not applicable
Amphotec	Injection, lipid complex	50 mg/10mL	Intravenous	InterMune, Inc.	2006-02-27	Not applicable
Amphotec	Injection, lipid complex	100 mg/100mg	Intravenous	Kadmon Pharmaceuticals	2005-05-20	2011-05-31
Amphotec	Injection, lipid complex	100 mg/20mL	Intravenous	InterMune, Inc.	2006-02-27	Not applicable
Amphotec	Injection, lipid complex	50 mg/50mg	Intravenous	Kadmon Pharmaceuticals	2005-05-20	2011-05-31
Amphotec 100 mg	Powder, for suspension	100 mg / vial	Intravenous	Three Rivers Pharmaceuticals Llc	2004-06-17	2013-08-22
Amphotec 50 mg	Powder, for suspension	50 mg / vial	Intravenous	Three Rivers Pharmaceuticals Llc	2007-02-26	2013-08-22
Amphotericin B for Injection, USP	Powder, for solution	50 mg / vial	Intravenous	Sterimax Inc	Not applicable	Not applicable

Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Amphotericin B	Injectable, liposomal	50 mg/1	Intravenous	Sun Pharmaceutical Industries, Inc.	2022-02-09	Not applicable
Amphotericin B	Injection, powder, lyophilized, for solution	50 mg/10mL	Intravenous	XGen Pharmaceuticals DJB, Inc.	1992-04-29	Not applicable
Fungizone	Injection, powder, lyophilized, for solution	50 mg/10mL	Intravenous	E.R. Squibb & Sons, L.L.C.	1966-03-01	2005-09-30

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End	Region	Image
Abelcet	Amphotericin B (5 mg/1mL) + DL-dimyristoylphosphatidylcholine (3.4 mg/1mL) + DL-dimyristoylphosphatidylglycerol (1.5 mg/1mL)	Injection	Intravenous	Leadiant Biosciences, Inc.	2010-10-18	Not applicable

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

External Links

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

Phase	Status	Purpose	Conditions	Count
4	Completed	Other	Obesity, Morbid	1
4	Completed	Prevention	Candidiasis	1
4	Completed	Prevention	Leukemias	1
4	Completed	Treatment	Candidemia / Candidiasis, Invasive	1
4	Completed	Treatment	Central Line Fungal Infections	1
4	Completed	Treatment	Fungal Infections / Fungus, Nail / Onychomycosis	1
4	Completed	Treatment	Fungal Infections / Liver Disease	1
4	Completed	Treatment	Invasive Aspergillosis	1
4	Completed	Treatment	Post Kala Azar Dermal Leishmaniasis	1
4	Completed	Treatment	Visceral Leishmaniasis	1

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

Form	Route	Strength
Injection	Intravenous
Suspension	Intravenous	5 mg / mL
Injection, suspension	Intravenous
Injection, solution, concentrate	Intravenous	5 MG/ML
Injection, powder, lyophilized, for solution	Intravenous	50 mg/12.5mL
Powder, for solution	Intravenous	50 mg / vial
Injection, powder, for solution	Parenteral
Injection, powder, for suspension	Intravenous
Injection, powder, for solution	Intravenous	50 mg
Powder	Intravenous
Lozenge	Oral
Tablet	Oral	100000 IU
Suspension	Oral
Powder, for solution
Solution		50 mg/1vial
Suspension	Intravenous	100 mg
Suspension	Intravenous	50 mg
Injection, powder, for solution	Intravenous
Injection, lipid complex	Intravenous	100 mg/100mg
Injection, lipid complex	Intravenous	100 mg/20mL
Injection, lipid complex	Intravenous	50 mg/50mg
Injection, lipid complex	Intravenous	50 mg/10mL
Powder, for suspension	Intravenous	100 mg / vial
Powder, for suspension	Intravenous	50 mg / vial
Injectable, liposomal	Intravenous	50 mg/1
Injection, powder, lyophilized, for solution	Intravenous
Ointment	Ophthalmic
Injection, powder, lyophilized, for solution	Intravenous	50 mg/10mL
Powder, for solution	Parenteral	50 MG
Injection	Intravenous
Injection, powder, lyophilized, for solution	Intravenous	50 mg
Powder	Intravenous	50 mg
Injection, powder, for suspension	Intravenous	50 mg
Cream	Vaginal
Powder	Intravenous	50 mg/1vial

Prices

Unit description	Cost	Unit
Ambisome 50 mg vial	188.4USD	vial
Amphotec 100 mg vial	160.0USD	vial
Amphotec 50 mg vial	93.33USD	vial
Fungizone Iv 50 mg/vial	72.5USD	vial
Amphotericin b powder	29.99USD	g
Amphotericin b 50 mg vial	24.5USD	vial
Abelcet 5 mg/ml vial p-f	12.0USD	ml

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
CA1339008	No	1997-03-25	2014-03-25
CA1336890	No	1995-09-05	2012-09-05
US6406713	No	2002-06-18	2019-06-18
US5874104	No	1999-02-23	2016-02-23
US5965156	No	1999-10-12	2016-10-12

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	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	0.0819 mg/mL	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 Å²	ChemAxon
Rotatable Bond Count	3	ChemAxon
Refractivity	244.67 m³·mol^-1	ChemAxon
Polarizability	99.4 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	0	ChemAxon
Rule of Five	No	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	-	0.9308
Blood Brain Barrier	-	0.9659
Caco-2 permeable	-	0.7539
P-glycoprotein substrate	Substrate	0.6404
P-glycoprotein inhibitor I	Non-inhibitor	0.7322
P-glycoprotein inhibitor II	Non-inhibitor	0.5977
Renal organic cation transporter	Non-inhibitor	0.9491
CYP450 2C9 substrate	Non-substrate	0.7992
CYP450 2D6 substrate	Non-substrate	0.8785
CYP450 3A4 substrate	Substrate	0.5496
CYP450 1A2 substrate	Non-inhibitor	0.9046
CYP450 2C9 inhibitor	Non-inhibitor	0.941
CYP450 2D6 inhibitor	Non-inhibitor	0.9444
CYP450 2C19 inhibitor	Non-inhibitor	0.921
CYP450 3A4 inhibitor	Non-inhibitor	0.9381
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.984
Ames test	Non AMES toxic	0.9133
Carcinogenicity	Non-carcinogens	0.9682
Biodegradation	Not ready biodegradable	0.9414
Rat acute toxicity	2.2357 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9777
hERG inhibition (predictor II)	Non-inhibitor	0.7887

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available

Targets

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Details1. Ergosterol

Kind

Small molecule

Organism

Candida albicans

Pharmacological action

Yes

Actions

Binder

References

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]
Baginski M, Czub J: Amphotericin B and its new derivatives - mode of action. Curr Drug Metab. 2009 Jun;10(5):459-69. [Article]
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 August 09, 2022 10:05

Amphotericin B

Identification

Structure for Amphotericin B (DB00681)

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Targets

References