Amphotericin B

Amphotericin B is an antifungal
medication used for serious fungal
infections and leishmaniasis.[1] The fungal
infections it is used to treat include
aspergillosis, blastomycosis, candidiasis,
coccidioidomycosis, and
cryptococcosis.[2] For certain infections it
is given with flucytosine.[3] It is typically
given by injection into a vein.[2]
 Amphotericin B

Clinical data
Trade names Fungizone, Mysteclin-F,
AmBisome, others

AHFS/Drugs.com Monograph
MedlinePlus a682643
License data US DailyMed: Amphotericin_B
Routes of usually I.V. (slow
administration
 infusion only)
ATC code A01AB04 (WHO )
A07AA07 (WHO ),
G01AA03 (WHO ),
J02AA01 (WHO )

Legal status
Legal status In general:
℞ (Prescription only)

Pharmacokinetic data
Bioavailability 100% (IV)
Metabolism kidney
Elimination half-life initial phase : 24 hours,
second phase : approx.
15 days

Excretion 40% found in urine

 after single cumulated
over several days
biliar excretion also
important
Identifiers

IUPAC name
(1R,3S,5R,6R,9R, 11R,15S,16R,17R,18S,19E,21E, 23E,25E,27E,29E,31E,33R,35S,36R,37S)- 33-[(3-am ino- 3,6-dide oxy- β-D-m annopyra
nosyl)oxy]- 1,3,5,6,9,11,17,37-oc tahydroxy- 15,16,18-trim e thyl- 13-oxo- 14,39-dioxabic yc lo [33.3.1] nonatriac onta- 19,21,2
3,25,27,29,31-he ptae ne - 36-c arboxylic ac id

CAS Number 1397-89-3  

PubChem CID 14956

DrugBank DB00681  

ChemSpider 10237579  

UNII 7XU7A7DROE
KEGG D00203  

ChEBI CHEBI:2682  

ChEMBL ChEMBL267345  
NIAID ChemDB 000096
CompTox Dashboard DTXSID9022601
(EPA)

ECHA InfoCard 100.014.311

Chemical and physical data

Formula C47H73NO17
Molar mass 924.091 g·mol−1
3D model (JSmol) Interactive image
Melting point 170 °C (338 °F)

SMILES
O=C(O)[C@ @ H]3[C@ @ H](O)C[C@ @ ]2(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=CC=CC=CC=CC=CC=CC=C[C@ H](O[C@ @ H]1O[C@ H](C)[C@ @ H](O)[C@ H](N)[C@ @ H]1
O)C[C@ @ H]3O2

InChI
InChI=1S /C47H73NO17/c 1-27-17-15-13-11-9-7-5-6-8-10-12-14-16-18-34(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-,3
4-,35+,36+,37-,38-,40+,41-,42+,43+,44-,46-,47+/m 0/s1 
Key:APKFDS VGJQXUKY-INPOYWNPS A-N 

  (verify)
Common side effects include a reaction
with fever, chills, and headaches soon
after the medication is given, as well as
kidney problems.[2] Allergic symptoms
including anaphylaxis may occur.[2] Other
serious side effects include low blood
potassium and inflammation of the
heart.[1] It appears to be relatively safe in
pregnancy.[2] There is a lipid formulation
that has a lower risk of side effects.[2] It is
in the polyene class of medications and
works in part by interfering with the cell
membrane of the fungus.[1][2]

Amphotericin B was isolated from

Streptomyces nodosus in 1955 and came
into medical use in 1958.[4][5] It is on the
World Health Organization's List of
Essential Medicines, the safest and most
effective medicines needed in a health
system.[6] It is available as a generic
medication.[2] The cost in the developing
world of a course of treatment as of 2010
is between US$162 and 229.[1]

Medical uses

Antifungal …

One of the main uses of amphotericin B is

treating a wide range of systemic fungal
infections. Due to its extensive side
effects, it is often reserved for severe
infections in critically ill, or
immunocompromised patients. It is
considered first line therapy for invasive
mucormycosis infections, cryptococcal
meningitis, and certain aspergillus and
candidal infections.[7][8] It has been a
highly effective drug for over fifty years in
large part because it has a low incidence
of drug resistance in the pathogens it
treats. This is because amphotericin B
resistance requires sacrifices on the part
of the pathogen that make it susceptible to
the host environment, and too weak to
cause infection.[9]
Antiprotozoal …

Amphotericin B is used for life-threatening

protozoan infections such as visceral
leishmaniasis[10] and primary amoebic
meningoencephalitis.[11]

Spectrum of susceptibility …

The following table shows the

amphotericin B susceptibility for a
selection of medically important fungi.
 Amphotericin B
Species
MIC breakpoint (mg/L)

Aspergillus fumigatus 1[12]

Aspergillus terreus Resist ant [12][13]

Candida albicans 1[12]

Candida krusei 1[12]

Candida glabrata 1[12]

Candida lusitaniae Int rinsically resist ant [13]

Cryptococcus neoformans 2[14]

Fusarium oxysporum 2[14]

Available formulations

Intravenous …

Amphotericin B alone is insoluble in normal

saline at a pH of 7. Therefore, several
formulations have been devised to
improve its intravenous bioavailability.[15]
Lipid-based formulations of amphotericin
B are no more effective than conventional
formulations, although there is some
evidence that lipid-based formulations
may be better tolerated by patients and
may have fewer adverse effects.[16]

Deoxycholate …

The original formulation uses sodium

deoxycholate to improve solubility.[13]
Amphotericin B deoxycholate (ABD) is
administered intravenously.[17] As the
original formulation of amphotericin, it is
often referred to as "conventional"
amphotericin.[18]

Liposomal …
In order to improve the tolerability of
amphotericin and reduce toxicity, several
lipid formulations have been developed.[13]
Liposomal formulations have been found
to have less renal toxicity than
deoxycholate,[19][20] and fewer infusion-
related reactions.[13] They are more
expensive than amphotericin B
deoxycholate.[21]

AmBisome (LAMB) is a liposomal

formulation of amphotericin B for injection
and consists of a mixture of
phosphatidylcholine, cholesterol and
distearoyl phosphatidylglycerol that in
aqueous media spontaneously arrange
into unilamellar vesicles that contain
amphotericin B.[13][22]

It was developed by NeXstar

Pharmaceuticals (acquired by Gilead
Sciences in 1999). It was approved by the
FDA in 1997.[23] It is marketed by Gilead in
Europe and licensed to Astellas Pharma
(formerly Fujisawa Pharmaceuticals) for
marketing in the US, and Sumitomo
Pharmaceuticals in Japan. Fungisome[24]
is a generic liposomal complex of
amphotericin B marketed by Lifecare
Innovations of India.Amphotericin is
available in by abbot india brand name
fungizone inj in 50 mg rs 367 per vial and
many other also like amphy by intas 2990
and lambin by sun Pharma 4457 etc all are
injection

Lipid complex formulations …

A number of lipid complex preparations

are also available. Abelcet was approved
by the FDA in 1995.[25] It consists of
amphotericin B and two lipids in a 1:1 ratio
that form large ribbon-like structures.[13]
Amphotec is a complex of amphotericin
and sodium cholesteryl sulfate in a 1:1
ratio. Two molecules of each form a
tetramer that aggregate into spiral arms on
a disk-like complex.[22] It was approved by
the FDA in 1996.[25]

By mouth …

An oral preparation exists but is not widely

available.[26] The amphipathic nature of
amphotericin along with its low solubility
and permeability has posed major hurdles
for oral administration given its low
bioavailability. In the past it had been used
for fungal infections of the surface of the
GI tract such as thrush, but has been
replaced by other antifungals such as
nystatin and fluconazole.[27]
However, recently novel nanoparticulate
drug delivery systems such as
AmbiOnp,[28] nanosuspensions, lipid-based
drug delivery systems including
cochleates, self-emulsifying drug delivery
systems,[29] solid lipid nanoparticles[30]
and polymeric nanoparticles[31]—such as
Amphotericin B in pegylated polylactide
coglycolide copolymer nanoparticles[32]—
have demonstrated potential for oral
formulation of amphotericin B.[33]

Side effects
Amphotericin B is well known for its severe
and potentially lethal side effects. Very
often, it causes a serious reaction soon
after infusion (within 1 to 3 hours),
consisting of high fever, shaking chills,
hypotension, anorexia, nausea, vomiting,
headache, dyspnea and tachypnea,
drowsiness, and generalized weakness.
The violent chills and fevers have caused
the drug to be nicknamed "shake and
bake".[34][35] This reaction sometimes
subsides with later applications of the
drug, and may in part be due to histamine
liberation. An increase in prostaglandin
synthesis may also play a role. This nearly
universal febrile response necessitates a
critical (and diagnostically difficult)
professional determination as to whether
the onset of high fever is a novel symptom
of a fast-progressing disease, or merely
the effect of the drug. To decrease the
likelihood and severity of the symptoms,
initial doses should be low, and increased
slowly. Paracetamol, pethidine,
diphenhydramine, and hydrocortisone have
all been used to treat or prevent the
syndrome, but the prophylactic use of
these drugs is often limited by the patient's
condition.

Intravenously administered amphotericin B

in therapeutic doses has also been
associated with multiple organ damage.
Kidney damage is a frequently reported
side effect, and can be severe and/or
irreversible. Less kidney toxicity has been
reported with liposomal formulations
(such as AmBisome) and it has become
preferred in patients with preexisting renal
injury.[36][37] The integrity of the liposome is
disrupted when it binds to the fungal cell
wall, but is not affected by the mammalian
cell membrane,[38] so the association with
liposomes decreases the exposure of the
kidneys to amphotericin B, which explains
its less nephrotoxic effects.[39]

In addition, electrolyte imbalances such as

hypokalemia and hypomagnesemia are
also common.[40] In the liver, increased
liver enzymes and hepatotoxicity (up to
and including fulminant liver failure) are
common. In the circulatory system, several
forms of anemia and other blood
dyscrasias (leukopenia, thrombopenia),
serious cardiac arrhythmias (including
ventricular fibrillation), and even frank
cardiac failure have been reported. Skin
reactions, including serious forms, are also
possible.

Interactions
Flucytosine: Toxicity of flucytosine is
increased and allows a lower dose of
amphotericin B. Amphotericin B may
also facilitate entry of flucystosine into
the fungal cell by interfering with the
permeability of the fungal cell
membrane.
Diuretics or cisplatin: Increased renal
toxicity and increased risk of
hypokalemia
Corticosteroids: Increased risk of
hypokalemia
Cytostatic drugs: Increased risk of
kidney damage, hypotension, and
bronchospasms
Other nephrotoxic drugs (such as
aminoglycosides): Increased risk of
serious renal damage
 Foscarnet, ganciclovir, tenofovir,
adefovir: Risk of hematological and
renal side effects of amphotericin B are
increased
Transfusion of leukocytes: Risk of
pulmonal (lung) damage occurs, space
the intervals between the application of
amphotericin B and the transfusion, and
monitor pulmonary function

Mechanism of action
Amphotericin B binds with ergosterol, a
component of fungal cell membranes,
forming pores that cause rapid leakage of
monovalent ions (K+, Na+, H+ and Cl−) and
subsequent fungal cell death. This is
amphotericin B's primary effect as an
antifungal agent.[41][42] It has been found
that the amphotericin B/ergosterol
bimolecular complex that maintains these
pores is stabilized by Van der Waals
interactions.[43] Researchers have found
evidence that amphotericin B also causes
oxidative stress within the fungal cell,[44]
but it remains unclear to what extent this
oxidative damage contributes to the drug's
effectiveness.[41] The addition of free
radical scavengers or antioxidants can
lead to amphotericin resistance in some
species, such as Scedosporium prolificans,
without affecting the cell wall.
Two amphotericins, amphotericin A and
amphotericin B, are known, but only B is
used clinically, because it is significantly
more active in vivo. Amphotericin A is
almost identical to amphotericin B (having
a C=C double bond between the 27th and
28th carbons), but has little antifungal
activity.[15]

Mechanism of toxicity
Mammalian and fungal membranes both
contain sterols, a primary membrane
target for amphotericin B. Because
mammalian and fungal membranes are
similar in structure and composition, this is
one mechanism by which amphotericin B
causes cellular toxicity. Amphotericin B
molecules can form pores in the host
membrane as well as the fungal
membrane. This impairment in membrane
barrier function can have lethal
effects.[44][45][46] Ergosterol, the fungal
sterol, is more sensitive to amphotericin B
than cholesterol, the common mammalian
sterol. Reactivity with the membrane is
also sterol concentration dependent.[47]
Bacteria are not affected as their cell
membranes do not contain sterols.

Amphotericin administration is limited by

infusion-related toxicity. This is thought to
result from innate immune production of
proinflammatory cytokines.[45][48]

Biosynthesis
The natural route to synthesis includes
polyketide synthase components.[49] The
carbon chains of Amphotericin B are
assembled from sixteen 'C2' acetate and
three 'C3'propionate units by polyketide
syntheses (PKSs).[50] Polyketide
biosynthesis begins with the
decarboxylative condensation of a
dicarboxylic acid extender unit with a
starter acyl unit to form a β-ketoacyl
intermediate. The growing chain is
constructed by a series of Claisen
reactions. Within each module, the
extender units are loaded onto the current
ACP domain by acetyl transferase (AT).
The ACP-bound elongation group reacts in
a Claisen condensation with the KS-bound
polyketide chain. Ketoreductase (KR),
dehydratase (DH) and enoyl reductase
(ER) enzymes may also be present to form
alcohol, double bonds or single bonds.[51]
After cyclisation, the macrolactone core
undergoes further modification by
hydroxylation, methylation and
glycosylation. The order of these
processes is unknown.
History
It was originally extracted from
Streptomyces nodosus, a filamentous
bacterium, in 1955, at the Squibb Institute
for Medical Research from cultures of an
undescribed streptomycete isolated from
the soil collected in the Orinoco River
region of Venezuela.[15][52] Two antifungal
substances were isolated from the soil
culture, Amphotericin A and Amphotericin
B, but B had better antifungal activity. For
decades it remained the only effective
therapy for invasive fungal disease until
the development of the azole antifungals
in the early 1980s.[17]
Its complete stereo structure was
determined in 1970 by an X-ray structure
of the N-iodoacetyl derivative.[53] The first
synthesis of the compound's naturally
occurring enantiomeric form was achieved
in 1987 by K. C. Nicolaou.[54]

Society and culture

Formulations …

It is a subgroup of the macrolide

antibiotics, and exhibits similar structural
elements.[55] Currently, the drug is
available in many forms. Either
"conventionally" complexed with sodium
deoxycholate (ABD), as a cholesteryl
sulfate complex (ABCD), as a lipid
complex (ABLC), and as a liposomal
formulation (LAMB). The latter
formulations have been developed to
improve tolerability and decrease toxicity,
but may show considerably different
pharmacokinetic characteristics compared
to conventional amphotericin B.[13]

Names …

Amphotericin name originates from the

chemical's amphoteric properties.
It is commercially known as: Fungilin,
Fungizone, Abelcet, AmBisome,
Fungisome, Amphocil, Amphotec,
Halizon[56]

References
1. World Health Organization (March 2010).
Control of the leishmaniasis: report of a
meeting of the WHO Expert Committee on
the Control of Leishmaniases. Geneva:
World Health Organization. pp. 55, 88, 186.
hdl:10665/44412 . ISBN 9789241209496.
2. "Amphotericin B" . The American Society of
Health-System Pharmacists. Archived
from the original on 2015-01-01. Retrieved
January 1, 2015.
3. World Health Organization (2009). Stuart
MC, Kouimtzi M, Hill SR (eds.). WHO Model
Formulary 2008. World Health
Organization. p. 145. hdl:10665/44053 .
ISBN 9789241547659.
4. Walker, S. R. (2012). Trends and Changes in
Drug Research and Development . Springer
Science & Business Media. p. 109.
ISBN 9789400926592. Archived from the
original on 2017-09-10.
5. Fischer, Jnos; Ganellin, C. Robin (2006).
Analogue-based Drug Discovery . John
Wiley & Sons. p. 477.
ISBN 9783527607495.
 . World Health Organization (2019). World
Health Organization model list of essential
medicines: 21st list 2019. Geneva: World
Health Organization. hdl:10665/325771 .
WHO/MVP/EMP/IAU/2019.06. License: CC
BY-NC-SA 3.0 IGO.
7. Raphael Dolin, MD; Martin j. Blaser, MD (28
August 2014). Drugs Active against Fungi,
Pneumocystis, and Microsporidia. pp. 479–
494.e4. ISBN 978-1-4557-4801-3. Missing
|author1= (help)
. Moen, Marit D.; Lyseng-Williamson,
Katherine A.; Scott, Lesley J. (2012-09-17).
"Liposomal Amphotericin B". Drugs. 69 (3):
361–392. doi:10.2165/00003495-
200969030-00010 . ISSN 0012-6667 .
PMID 19275278 . S2CID 34340503 .
 9. Rura, Nicole (2013-10-29). "Understanding
the evolution of drug resistance points to
novel strategy for developing better
antimicrobials" . Archived from the
original on 2016-11-15. Retrieved
2016-11-14 – via Whitehead Institute.
10. den Boer, Margriet; Davidson, Robert N.
(2006-04-01). "Treatment options for
visceral leishmaniasis". Expert Review of
Anti-Infective Therapy. 4 (2): 187–197.
doi:10.1586/14787210.4.2.187 .
ISSN 1744-8336 . PMID 16597201 .
S2CID 42784356 .
11. Grace, Eddie; Asbill, Scott; Virga, Kris
(November 2015). "Naegleria fowleri:
Pathogenesis, Diagnosis, and Treatment
Options" . Antimicrobial Agents and
Chemotherapy. 59 (11): 6677–6681.
doi:10.1128/AAC.01293-15 .
PMC 4604384 . PMID 26259797 .
12. "European Committee on Antimicrobial
Susceptibility Testing: Antifungal Agents,
Breakpoint tables for interpretation of
MICs" (PDF). 2015-11-16. Retrieved
2015-11-17.
13. Hamill, Richard J. (2013-06-01).
"Amphotericin B Formulations: A
Comparative Review of Efficacy and
Toxicity". Drugs. 73 (9): 919–934.
doi:10.1007/s40265-013-0069-4 .
ISSN 0012-6667 . PMID 23729001 .
S2CID 2785865 .
14. "Index | The Antimicrobial Index
Knowledgebase - TOKU-E" .
antibiotics.toku-e.com. Archived from the
original on 2015-11-09. Retrieved
2015-11-17.
15. Dutcher, James D. (1968-10-01). "THe
discovery and development of
amphotericin b". Chest. 54 (Supplement_1):
296–298.
doi:10.1378/chest.54.Supplement_1.296 .
ISSN 0012-3692 . PMID 4877964 .
1 . Steimbach, Laiza M., Fernanda S. Tonin,
Suzane Virtuoso, Helena HL Borba, Andréia
CC Sanches, Astrid Wiens, Fernando
Fernandez‐Llimós, and Roberto Pontarolo.
"Efficacy and safety of amphotericin B lipid‐
based formulations—A systematic review
and meta‐analysis." Mycoses 60, no. 3
(2017): 146-154.
17. Maertens, J. A. (2004-03-01). "History of
the development of azole derivatives".
Clinical Microbiology and Infection. 10: 1–
10. doi:10.1111/j.1470-
9465.2004.00841.x . ISSN 1469-0691 .
PMID 14748798 .
1 . Clemons, KV; Stevens, DA (April 1998).
"Comparison of Fungizone, Amphotec,
AmBisome, and Abelcet for Treatment of
Systemic Murine Cryptococcosis" .
Antimicrobial Agents and Chemotherapy.
42 (4): 899–902.
doi:10.1128/AAC.42.4.899 . PMC 105563 .
PMID 9559804 .
19. Botero Aguirre, Juan Pablo; Restrepo
Hamid, Alejandra Maria (2015-11-23).
"Amphotericin B deoxycholate versus
liposomal amphotericin B: Effects on
kidney function". Cochrane Database of
Systematic Reviews (11): CD010481.
doi:10.1002/14651858.cd010481.pub2 .
PMID 26595825 .
20. Mistro, Sóstenes; Maciel, Isis de M.;
Menezes, Rouseli G. de; Maia, Zuinara P.;
Schooley, Robert T.; Badaró, Roberto (2012-
06-15). "Does Lipid Emulsion Reduce
Amphotericin B Nephrotoxicity? A
Systematic Review and Meta-analysis" .
Clinical Infectious Diseases. 54 (12):
1774–1777. doi:10.1093/cid/cis290 .
ISSN 1058-4838 . PMID 22491505 .
21. Bennett, John (2000-11-15). "Editorial
Response: Choosing Amphotericin B
Formulations—Between a Rock and a Hard
Place" . Clinical Infectious Diseases. 31 (5):
1164–1165. doi:10.1086/317443 .
ISSN 1058-4838 . PMID 11073746 .
22. Slain, Douglas (1999-03-01). "Lipid-Based
Amphotericin B for the Treatment of Fungal
Infections". Pharmacotherapy. 19 (3): 306–
323. doi:10.1592/phco.19.4.306.30934 .
ISSN 1875-9114 . PMID 10221369 .
S2CID 43479677 .
23. "Drug Approval Package" .
www.accessdata.fda.gov. Archived from
the original on 2015-11-17. Retrieved
2015-11-03.
24. "Untitled Document" .
www.fungisome.com. Archived from the
original on 2015-12-27. Retrieved
2015-11-03.
25. "Drugs@FDA: FDA Approved Drug
Products" . www.accessdata.fda.gov.
Archived from the original on 2014-08-13.
Retrieved 2015-11-03.
2 . Wasan KM, Wasan EK, Gershkovich P, et al.
(2009). "Highly Effective oral amphotericin
B formulation against murine visceral
leishmaniasis" . J Infect Dis. 200 (3): 357–
360. doi:10.1086/600105 .
PMID 19545212 .
27. Pappas, Peter G.; Kauffman, Carol A.;
Andes, David; Benjamin, Daniel K.;
Calandra, Thierry F.; Edwards, John E.; Filler,
Scott G.; Fisher, John F.; Kullberg, Bart-Jan
(2009-03-01). "Clinical practice guidelines
for the management of candidiasis: 2009
update by the Infectious Diseases Society
of America" . Clinical Infectious Diseases.
48 (5): 503–535. doi:10.1086/596757 .
ISSN 1537-6591 . PMC 7294538 .
PMID 19191635 .
2 . Patel, Pratikkumar A.; Patravale, Vandana
B. (2011). "AmbiOnp: solid lipid
nanoparticles of amphotericin B for oral
administration". Journal of Biomedical
Nanotechnology. 7 (5): 632–639.
doi:10.1166/jbn.2011.1332 .
PMID 22195480 .
29. Wasan, EK; Bartlett, K; Gershkovich, P;
Sivak, O; Banno, B; Wong, Z; Gagnon, J;
Gates, B; Leon, CG; Wasan, KM (2009).
"Development and characterization of oral
lipid-based amphotericin B formulations
with enhanced drug solubility, stability and
antifungal activity in rats infected with
Aspergillus fumigatus or Candida albicans".
International Journal of Pharmaceutics.
372 (1–2): 76–84.
doi:10.1016/j.ijpharm.2009.01.003 .
PMID 19236839 .
30. Patel, PA; Patravale, VB (2011). "AmbiOnp:
solid lipid nanoparticles of amphotericin B
for oral administration". Journal of
Biomedical Nanotechnology. 7 (5): 632–
639. doi:10.1166/jbn.2011.1332 .
PMID 22195480 .
31. Italia, JL; Yahya, MM; Singh, D (2009).
"Biodegradable nanoparticles improve oral
Bioavailability of Amphotericin B and Show
Reduced Nephrotoxicity Compared to
Intravenous Fungizone®". Pharmaceutical
Research. 26 (6): 1324–1331.
doi:10.1007/s11095-009-9841-2 .
PMID 19214716 . S2CID 8612917 .
32. AL-Quadeib, Bushra T.; Radwan, Mahasen
A.; Siller, Lidija; Horrocks, Benjamin; Wright,
Matthew C. (2015-07-01). "Stealth
Amphotericin B nanoparticles for oral drug
delivery: In vitro optimization" . Saudi
Pharmaceutical Journal. 23 (3): 290–302.
doi:10.1016/j.jsps.2014.11.004 .
PMC 4475820 . PMID 26106277 .
33. Patel P.A., Fernandes C.B., Pol A.S.,
Patravale V.B. Oral Amphotericin B:
challenges and avenues. Int. J. Pharm.
Biosci. Technol. 2013;1:1–9.
34. "Shake and Bake" . TheFreeDictionary.com.
Retrieved 2016-12-09.
35. Hartsel, Scott. "Studies on Amphotericin B"
(PDF). Archived (PDF) from the original on
20 December 2016. Retrieved 8 December
2016.
3 . Walsh, Thomas J.; Finberg, Robert W.;
Arndt, Carola; Hiemenz, John; Schwartz,
Cindy; Bodensteiner, David; Pappas, Peter;
Seibel, Nita; Greenberg, Richard N. (1999-
03-11). "Liposomal Amphotericin B for
Empirical Therapy in Patients with
Persistent Fever and Neutropenia". New
England Journal of Medicine. 340 (10):
764–771.
doi:10.1056/NEJM199903113401004 .
ISSN 0028-4793 . PMID 10072411 .
37. Perfect, John R.; Dismukes, William E.;
Dromer, Francoise; Goldman, David L.;
Graybill, John R.; Hamill, Richard J.;
Harrison, Thomas S.; Larsen, Robert A.;
Lortholary, Olivier (2010-02-01). "Clinical
Practice Guidelines for the Management of
Cryptococcal Disease: 2010 Update by the
Infectious Diseases Society of America" .
Clinical Infectious Diseases. 50 (3): 291–
322. doi:10.1086/649858 . ISSN 1058-
4838 . PMC 5826644 . PMID 20047480 .
3 . Jill Adler-Moore,* and Richard T. liposomal
formulation, structure, mechanism of action
and pre-clinical experience. Journal of
Antimicrobial Chemotherapy (2002) 49,
21–30
39. J. Czub, M. Baginski. Amphotericin B and
Its New Derivatives Mode of action.
Department of pharmaceutical Technology
and Biochemistry. Faculty of Chemistry,
Gdnsk University of Technology. 2009, 10-
459-469.
40. Zietse, R.; Zoutendijk, R.; Hoorn, E. J.
(2009). "Fluid, electrolyte and acid–base
disorders associated with antibiotic
therapy". Nature Reviews Nephrology. 5 (4):
193–202. doi:10.1038/nrneph.2009.17 .
PMID 19322184 . S2CID 24486546 .
41. Mesa-Arango, Ana Cecilia; Scorzoni, Liliana;
Zaragoza, Oscar (2012-01-01). "It only
takes one to do many jobs: Amphotericin B
as antifungal and immunomodulatory
drug" . Frontiers in Microbiology. 3: 286.
doi:10.3389/fmicb.2012.00286 .
PMC 3441194 . PMID 23024638 .
42. O'Keeffe, Joseph; Doyle, Sean; Kavanagh,
Kevin (2003-12-01). "Exposure of the yeast
Candida albicans to the anti-neoplastic
agent adriamycin increases the tolerance to
amphotericin B" (PDF). Journal of
Pharmacy and Pharmacology. 55 (12):
1629–1633.
doi:10.1211/0022357022359 . ISSN 2042-
7158 . PMID 14738588 .
S2CID 38893122 .
43. "Molecular modelling of amphotericin B-
ergosterol primary complex in water II".
Biophysical Chemistry. 141.
44. Baginski, M.; Czub, J. (2009). "Amphotericin
B and Its New Derivatives–Mode of Action".
Current Drug Metabolism. 10 (5): 459–69.
doi:10.2174/138920009788898019 .
PMID 19689243 .
45. Laniado-Laborin R. and Cabrales-Vargas
MN. Amphotericin B: side effects and
toxicity. Revista Iberoamericana de
Micologia. (2009): 223–7.
4 . Pfizer. Amphocin. Accessed at "Archived
copy" (PDF). Archived from the original
(PDF) on 2011-04-19. Retrieved
2010-02-18. on Feb 18 2010.
47. Vertut-Croquin, Aline; Bolard, Jacques;
Chabbert, Marie; Gary-Bobo, Claude (1983).
"Differences in the Interaction of the
Polyene Antibiotic Amphotericin B with
Cholesterol- or Ergosterol-Containing
Phospholipid Vesicles. A Circular
Dichroism and Permeability Study".
Biochemistry. 22 (12): 2939–2944.
doi:10.1021/bi00281a024 .
PMID 6871175 .
4 . Drew, R. Pharmacology of amphotericin B.
Uptodate. Sep 2009. Accessed at
http://www.utdol.com/online/content/topic
.do?
topicKey=antibiot/4619&selectedTitle=2~1
50&source=search_result on Feb 18 2010.
49. Khan N, Rawlings B, Caffrey P (2011-01-
26). "A labile point in mutant amphotericin
polyketide synthases" . Biotechnol. Lett. 33
(6): 1121–6. doi:10.1007/s10529-011-
0538-3 . PMID 21267757 .
S2CID 10209476 .
50. McNamara, Carmel M.; Box, Stephen;
Crawforth, James M.; Hickman, Benjamin
S.; Norwood, Timothy J. (1998-01-01).
"Biosynthesis of amphotericin B" (PDF).
Journal of the Chemical Society, Perkin
Transactions 1 (1): 83–88.
doi:10.1039/A704545J . hdl:2381/33805 .
51. Caffrey, Patrick; Lynch, Susan; Flood,
Elizabeth; Finnan, Shirley; Oliynyk, Markiyan
(2001). "Amphotericin biosynthesis in
Streptomyces nodosus: deductions from
analysis of polyketide synthase and late
genes" . Chemistry & Biology. 8 (7): 713–
723. doi:10.1016/S1074-5521(01)00046-
1 . PMID 11451671 .
52. Procópio RE, Silva IR, Martins MK, Azevedo
JL, Araújo JM (2012). "Antibiotics produced
by Streptomyces" . The Brazilian Journal of
Infectious Diseases. 16 (5): 466–71.
doi:10.1016/j.bjid.2012.08.014 .
PMID 22975171 .
53. McNamara, Carmel M.; Box, Stephen;
Crawforth, James M.; Hickman, Benjamin
S.; Norwood, Timothy J.; Rawlings, Bernard
J. (1998). "Biosynthesis of amphotericin B".
Journal of the Chemical Society, Perkin
Transactions 1. 0 (1): 83–88.
doi:10.1039/a704545j . hdl:2381/33805 .
54. Nicolaou, K. C.; Daines, R. A.; Chakraborty,
T. K.; Ogawa, Y. (1987-04-01). "Total
synthesis of amphotericin B". Journal of the
American Chemical Society. 109 (9):
2821–2822. doi:10.1021/ja00243a043 .
ISSN 0002-7863 .
55. "Chemistry and Biology of the Polyene
Macrolide Antibiotics". Bacteriological
Reviews. 32.
5 . "Halizon" . Edu.drugs. Archived from the
original on 2016-11-15. Retrieved
2016-11-14.

External links
"Amphotericin B" . Drug Information
Portal. U.S. National Library of Medicine.
AmBisome Summaries of Product
Characteristics (United Kingdom)
Amphotericin B
"Amphotericin B Liposomal Injection" .
MedlinePlus.
"Amphotericin B Lipid Complex
Injection" . MedlinePlus.
Retrieved from
"https://en.wikipedia.org/w/index.php?
title=Amphotericin_B&oldid=1023100803"

Last edited 4 days ago by Imransaifi mrt

Content is available under CC BY-SA 3.0 unless

otherwise noted.