Nystatin: Difference between revisions

{{Short description|Antifungal medication}}

{{Use dmy dates|date=March 2024}}

{{cs1 config|name-list-style=vanc|display-authors=6}}

{{Infobox drug

| verifiedrevid = 458776717

| image = Nystatin.svg

| width = 300

| alt =

| image2 = Nystatin ball-and-stick.png

| alt2 =

<!-- Clinical data -->

| pronounce =

| tradename = Mycostatin, others<ref name=AHFS2016/>

| DailyMedID = Nystatin

| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->

| pregnancy_AU_comment =

| pregnancy_category =

| routes_of_administration = [[Topical administration|Topical]], [[Vaginal administration|vaginal]], [[by mouth]]

| class = [[Polyene antimycotic|Polyene]] [[antifungal medication]]<ref name="AHFS2016" />

| ATC_prefix = A07

| ATC_suffix = AA02

| ATC_supplemental = {{ATC|D01|AA01}} {{ATC|G01|AA01}}

<!-- Legal status -->

| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled -->

| legal_AU_comment =

| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->

| legal_BR_comment =

| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->

| legal_CA_comment =

| legal_DE = <!-- Anlage I, II, III or Unscheduled -->

| legal_DE_comment =

| legal_NZ = <!-- Class A, B, C -->

| legal_NZ_comment =

| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->

| legal_UK_comment =

| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->

| legal_US_comment =

| legal_EU =

| legal_EU_comment =

| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->

| legal_UN_comment =

| legal_status = Rx-only

<!-- Pharmacokinetic data -->

| protein_bound =

| metabolism = None (not extensively absorbed)

| metabolites =

| onset =

| elimination_half-life = Dependent upon GI transit time

| duration_of_action =

| excretion = Fecal (100%)

<!-- Identifiers -->

| IUPHAR_ligand =

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID = 23078586

| UNII_Ref = {{fdacite|correct|FDA}}

| KEGG_Ref = {{keggcite|correct|kegg}}

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 229383

| NIAID_ChemDB = 004993

| PDB_ligand =

| synonyms =

<!-- Chemical and physical data -->

| IUPAC_name = (1''S'',3''R'',4''R'',7''R'',9''R'',11''R'',15''S'',16''R'',17''R'',18''S'',19''E'',21''E'', 25''E'',27''E'',29''E'',31''E'',33''R'',35''S'',36''R'',37''S'')-33-[(3-amino-3,6-dideoxy-β-<small>L</small>-mannopyranosyl)oxy]-1, 3,4,7,9,11,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14, 39-dioxabicyclo[33.3.1]nonatriaconta-19,21,25,27,29,31-hexaene-36-carboxylic acid

| C=47 | H=75 | N=1 | O=17

| SMILES = CC1C=CC=CCCC=CC=CC=CC=CC(CC2C(C(CC(O2)(CC(C(CCC(CC(CC(CC(=O)OC(C(C1O)C)C)O)O)O)O)O)O)O)C(=O)O)OC3C(C(C(C(O3)C)O)N)O

| StdInChI_Ref = {{stdinchicite|changed|chemspider}}

| StdInChI = 1S/C47H75NO17/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)25-36(53)35(52)20-19-31(49)21-32(50)22-33(51)23-39(55)62-29(3)28(2)42(27)56/h5-6,8,10-18,27-38,40-44,46,49-54,56-58,61H,7,9,19-26,48H2,1-4H3,(H,59,60)/b6-5+,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

| StdInChI_comment =

| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}

| StdInChIKey = VQOXZBDYSJBXMA-NQTDYLQESA-N

| density =

| density_notes =

| melting_point = 44-46

| melting_high =

| melting_notes =

| boiling_point =

| boiling_notes =

| solubility =

| sol_units =

| specific_rotation =

<!-- Definition and medical uses -->

'''Nystatin''', sold under the brand name '''Mycostatin''' among others, is an [[antifungal medication]].<ref name=AHFS2016/> It is used to treat ''[[Candida (fungus)|Candida]]'' infections of the skin including [[diaper rash]], [[Candidiasis|thrush]], [[esophageal candidiasis]], and [[vaginal yeast infections]].<ref name="AHFS2016" /> It may also be used to prevent candidiasis in those who are at high risk.<ref name=AHFS2016/> Nystatin may be used by mouth, in the vagina, or applied to the skin.<ref name=AHFS2016>{{cite web|title=Nystatin|url=https://www.drugs.com/monograph/nystatin.html|publisher=[[American Society of Health-System Pharmacists]]|access-date=27 January 2016|url-status=live|archive-url=https://web.archive.org/web/20160203230150/http://www.drugs.com/monograph/nystatin.html|archive-date=3 February 2016}}</ref>

<!-- Side effects and mechanism -->

Common side effects when applied to the skin include burning, itching, and a rash.<ref name=AHFS2016/> Common side effects when taken by mouth include vomiting and diarrhea.<ref name=AHFS2016/> During [[pregnancy]] use in the vagina is safe while other formulations have not been studied in this group.<ref name=AHFS2016/> It works by disrupting the [[cell membrane]] of the fungal cells.<ref name=AHFS2016/>

<!-- History, society and culture -->

Nystatin was discovered in 1950 by [[Rachel Fuller Brown]] and [[Elizabeth Lee Hazen]].<ref name=Es2013>{{cite book| vauthors = Espinel-Ingroff AV |title=Medical Mycology in the United States a Historical Analysis (1894-1996) |date=2013 |publisher=Springer Netherlands |location=Dordrecht |isbn=9789401703116 |page=62 |url=https://books.google.com/books?id=wE3qCAAAQBAJ&pg=PA62 |url-status=live|archive-url= https://web.archive.org/web/20160202112630/https://books.google.ca/books?id=wE3qCAAAQBAJ&pg=PA62 |archive-date=2 February 2016}}</ref> It was the first polyene macrolide antifungal.<ref>{{cite journal | vauthors = Gupte M, Kulkarni P, Ganguli BN | title = Antifungal antibiotics | journal = Applied Microbiology and Biotechnology | volume = 58 | issue = 1 | pages = 46–57 | date = January 2002 | pmid = 11831475 | doi = 10.1007/s002530100822 | s2cid = 8015426 }}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06 | hdl-access=free }}</ref> It is available as a [[generic medication]].<ref name=AHFS2016/> It is made from the bacterium ''[[Streptomyces noursei]]''.<ref name=Es2013/> In 2021, it was the 233rd most commonly prescribed medication in the United States, with more than one million prescriptions.<ref>{{cite web | title=The Top 300 of 2021 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=14 January 2024 | archive-date=15 January 2024 | archive-url=https://web.archive.org/web/20240115223848/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Nystatin - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Nystatin | access-date = 14 January 2024}}</ref>

== Medical uses ==

[[Skin]], [[vagina]]l, [[mouth]], and [[esophagus|esophageal]] ''[[Candida (genus)|Candida]]'' infections usually respond well to treatment with nystatin. Infections of nails or [[hyperkeratinization|hyperkeratinized]] skin do not respond well.<ref name=":1">{{Cite book|title=Goodman & Gilman's the Pharmacological Basis of Therapeutics| veditors =Brunton LL, Knollmann BC, Hilal-Dandan R |isbn=978-1-259-58473-2|edition=Thirteenth|location= New York | publisher = McGraw Hill / Medical |oclc=994570810| vauthors = Hilal-Dandan R, Knollmann B, Brunton L | date=5 December 2017}}</ref>

When given parenterally, its activity is reduced due to presence of plasma.<ref>{{Cite book|title=Pharmacology and Pharmacotherapeutics | vauthors = Satoskar RS, Rege N, Bhandarkar SD |date=2015|publisher=Elsevier | location = Chennai |isbn=978-8131243619 |oclc=978526697}}</ref>

Oral nystatin is often used as a preventive treatment in people who are at risk for fungal infections, such as [[AIDS]] patients with a low CD4⁺ count and people receiving [[chemotherapy]]. It has been investigated for use in patients after liver transplantation, but [[fluconazole]] was found to be much more effective for preventing colonization, invasive infection, and death.<ref name="pmid25188770">{{cite journal | vauthors = Gøtzsche PC, Johansen HK | title = Nystatin prophylaxis and treatment in severely immunodepressed patients | journal = The Cochrane Database of Systematic Reviews | volume = 2014 | issue = 9 | pages = CD002033 | date = September 2014 | pmid = 25188770 | pmc = 6457783 | doi = 10.1002/14651858.CD002033.pub2 }}</ref> It is effective in treating oral candidiasis in elderly people who wear dentures.<ref name=":0">{{cite journal | vauthors = Lyu X, Zhao C, Yan ZM, Hua H | title = Efficacy of nystatin for the treatment of oral candidiasis: a systematic review and meta-analysis | journal = Drug Design, Development and Therapy | volume = 10 | pages = 1161–1171 | date = 2016 | pmid = 27042008 | pmc = 4801147 | doi = 10.2147/DDDT.S100795 | doi-access = free }}</ref>

It is also used in very low birth-weight (less than 1500 g or 3&nbsp;lb 5oz o) infants to prevent invasive fungal infections, although fluconazole is the preferred treatment. It has been found to reduce the rate of invasive fungal infections and also reduce deaths when used in these babies.<ref>{{cite journal | vauthors = Pappas PG, Kauffman CA, Andes D, Benjamin DK, Calandra TF, Edwards JE, Filler SG, Fisher JF, Kullberg BJ, Ostrosky-Zeichner L, Reboli AC, Rex JH, Walsh TJ, Sobel JD | title = Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America | journal = Clinical Infectious Diseases | volume = 48 | issue = 5 | pages = 503–535 | date = March 2009 | pmid = 19191635 | pmc = 7294538 | doi = 10.1086/596757 | doi-access = free }}</ref>

Liposomal nystatin is not commercially available, but investigational use has shown greater ''in vitro'' activity than colloidal formulations of [[amphotericin B]], and demonstrated effectiveness against some amphotericin B-resistant forms of fungi.<ref name="Dismukes 50–53"/> It offers an intriguing possibility for difficult-to-treat systemic infections, such as invasive aspergillosis, or infections that demonstrate resistance to amphotericin B. ''[[Cryptococcus (fungus)|Cryptococcus]]'' is also sensitive to nystatin. Additionally, liposomal nystatin appears to cause fewer cases of and less severe nephrotoxicity than observed with amphotericin B.<ref name="Dismukes 50–53"/> <!-- when? At the time of this writing, plans for additional development and investigation of liposomal nystatin appear in flux. -->

==Adverse effects==

Bitter taste and nausea are more common than most other adverse effects.<ref name=":1" />

The oral suspension form produces a number of adverse effects including but not limited to:<ref>{{cite web | title = Nystatin (Oral route) | work = Micromedex Detailed Drug Information | publisher = PubMed Health, U.S. National Library of Medicine |url=https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0044680/#DDIC601025.side_effects_section|access-date=1 April 2014|url-status=live|archive-url=https://web.archive.org/web/20131221105109/http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0044680/#DDIC601025.side_effects_section|archive-date=21 December 2013}}</ref>

# Diarrhea

# Abdominal pain

# Rarely, tachycardia, bronchospasm, facial swelling, muscle aches

Both the oral suspension and the topical form can cause:

# Hypersensitivity reactions, including [[Stevens–Johnson syndrome]] in some cases<ref>{{cite web|title=FDA approved package insert|url=http://www.accessdata.fda.gov/drugsatfda_docs/anda/98/64142ap_appltr_prntlbl_chemr.pdf|url-status=live|archive-url=https://web.archive.org/web/20140421082418/http://www.accessdata.fda.gov/drugsatfda_docs/anda/98/64142ap_appltr_prntlbl_chemr.pdf|archive-date=21 April 2014}}</ref>

# Rash, itching, burning and acute generalized [[exanthem]]atous [[pustulosis]]<ref name="pmid9675578">{{cite journal | vauthors = Rosenberger A, Tebbe B, Treudler R, Orfanos CE | title = [Acute generalized exanthematous pustulosis, induced by nystatin] | language = de | journal = Der Hautarzt; Zeitschrift Fur Dermatologie, Venerologie, und Verwandte Gebiete | volume = 49 | issue = 6 | pages = 492–495 | date = June 1998 | pmid = 9675578 | doi = 10.1007/s001050050776 | s2cid = 10935411 }}</ref>

Too high of a dosage can potentially lead to additional side effects such as:<ref name=":2">{{Citation | vauthors = Groll AH, Piscitelli SC, Walsh TJ |title=Clinical Pharmacology of Systemic Antifungal Agents: A Comprehensive Review of Agents in Clinical Use, Current Investigational Compounds, and Putative Targets for Antifungal Drug Development |date=1 January 1998 |url=https://www.sciencedirect.com/science/article/pii/S1054358908601295 |volume=44 |pages=343–500 | veditors = August JT, Anders MW, Murad F, Coyle JT |access-date=9 December 2023 |publisher=Academic Press |series=Advances in Pharmacology |doi=10.1016/S1054-3589(08)60129-5 |pmid=9547888 |isbn=9780120329458 }}</ref>

# Nephrotoxicity

# Hypokalemia

# Chills and skin rash

Like [[amphotericin B]] and [[natamycin]], nystatin is an [[ionophore]].<ref>{{Cite book|title=Rang and Dale's pharmacology| vauthors = Rang HP, Dale MM, Flower RJ, Henderson G |isbn=978-0-7020-5362-7|edition=Eighth|location=[United Kingdom] | publisher = Churchill Livingstone |oclc=903083639|date = 21 January 2015}}</ref> It binds to [[ergosterol]], a major component of the fungal [[cell membrane]]. When present in sufficient concentrations, it forms pores in the membrane that lead to [[potassium|K⁺]] leakage, acidification, and death of the fungus.<ref>{{cite book| vauthors = Hammond SM |title=Biological activity of polyene antibiotics|series=Progress in Medicinal Chemistry|year=1977|volume=14|issue=105–179|pmid=345355|pages=105–79|doi=10.1016/S0079-6468(08)70148-6|isbn=9780720406450}}</ref> Ergosterol is a [[sterol]] unique to fungi, so the drug does not have such catastrophic effects on animals or plants. However, many of the systemic/toxic effects of nystatin in humans are attributable to its binding to mammalian sterols, namely [[cholesterol]]. This is the effect that accounts for the [[nephrotoxicity]] observed when high serum levels of nystatin are achieved.<ref name=":2" /> Despite the molecular similarities and differences of ergosterol and cholesterol, there is currently no consensus as to why nystatin has a higher binding affinity for ergosterol because it remains unclear how the nystatin pores are formed.<ref name=":2" /> Researchers have concluded thus far that nystatin pores are formed from 4-12 nystatin molecules, with an unknown number of the necessary sterol interactions.<ref>{{cite journal | vauthors = Helrich CS, Schmucker JA, Woodbury DJ | title = Evidence that nystatin channels form at the boundaries, not the interiors of lipid domains | journal = Biophysical Journal | volume = 91 | issue = 3 | pages = 1116–1127 | date = August 2006 | pmid = 16679364 | pmc = 1563755 | doi = 10.1529/biophysj.105.076281 | bibcode = 2006BpJ....91.1116H }}</ref>

Nystatin also impacts cell membrane potential and transport by [[lipid peroxidation]].<ref>{{cite journal | vauthors = Welman E, Peters TJ | title = Properties of lysosomes in guinea pig heart: subcellular distribution and in vitro stability | journal = Journal of Molecular and Cellular Cardiology | volume = 8 | issue = 6 | pages = 443–463 | date = June 1976 | pmid = 7679 | pmc = 1262305 | doi = 10.1016/S0006-3495(93)81343-2 | bibcode = 1993BpJ....64...92B }}</ref> [[Conjugated system|Conjugated]] double bonds in nystatin's structure steal [[electron density]] from ergosterol in fungal cell membranes. Lipid peroxidation alters the [[Hydrophile|hydrophilicity]] of the interior of [[Membrane channel|channels]] in the membrane, which is necessary to transport ions and [[Polar molecule|polar]] molecules. Disruption of [[membrane transport]] from nystatin results in rapid cell death. Lipid peroxidation by nystatin also contributes significantly to [[potassium|K⁺]] leakage due to structural modifications of the membrane.<ref>{{cite journal | vauthors = Stark G | title = The effect of ionizing radiation on lipid membranes | journal = Biochimica et Biophysica Acta (BBA) - Reviews on Biomembranes | volume = 1071 | issue = 2 | pages = 103–122 | date = July 1991 | pmid = 1854791 | doi = 10.1016/0304-4157(91)90020-w }}</ref>

==Biosynthesis==

Nystatin A₁ (often called nystatin) is biosynthesized by a bacterial strain, ''[[Streptomyces noursei]]''.<ref name="pmid15700127">{{cite journal | vauthors = Fjaervik E, Zotchev SB | title = Biosynthesis of the polyene macrolide antibiotic nystatin in Streptomyces noursei | journal = Applied Microbiology and Biotechnology | volume = 67 | issue = 4 | pages = 436–443 | date = June 2005 | pmid = 15700127 | doi = 10.1007/s00253-004-1802-4 | s2cid = 19291518 }}</ref> The structure of this active compound is characterized as a polyene macrolide with a deoxysugar <small>D</small>-[[mycosamine]], an [[aminoglycoside]].<ref name="pmid15700127"/> The genomic sequence of nystatin reveals the presence of the polyketide loading module (nysA), six polyketide syntheses modules (nysB, nysC, nysI, nysJ, and nysK) and two thioesterase modules (nysK and nysE).<ref name="pmid15700127"/> It is evident that the biosynthesis of the macrolide functionality follows the [[polyketide synthase]] I pathway.<ref>{{cite book| vauthors = Dewick PM |title=Medicinal Natural Products: A Biosynthetic Approach (3rd ed.)|year=2009|publisher=John Wiley & Sons Ltd|location=UK|isbn=978-0-471-97478-9}}</ref>

Following the biosynthesis of the macrolide, the compound undergoes post-synthetic modifications, which are aided by the following enzymes: GDP-mannose dehydratase (nysIII), P450 monooxygenase (nysL and nysN), aminotransferase (nysDII), and glycosyltransferase (nysDI).<ref name="pmid15700127"/> The biosynthetic pathway is thought to proceed as shown to yield nystatin.

<gallery>

File:L-5.gif|Loading to 5

File:Mod6-12.jpg|Modules 6-12

File:M13-18.gif|Modules 13 -18

File:Completed nystatin biosynthesis.jpg|Completed molecule

</gallery>The melting point of nystatin is 44 - 46&nbsp;°C.<ref>{{cite journal | vauthors = Elsner Z, Leszczyńska-Bakal H, Pawlak E, Smazyński T | title = Gel with nystatin for treatment of lung mycosis | journal = Polish Journal of Pharmacology and Pharmacy | volume = 28 | issue = 4 | pages = 349–352 | date = 1976 | pmid = 981024 }}</ref>

==History==

[[File:Elizabeth Lee Hazen Rachel Fuller Brown 1950s.jpg|thumb|Elizabeth Lee Hazen (left) and Rachel Fuller Brown in 1955.]]

Like many other antifungals and antibiotics, nystatin has [[bacteria]]l origin. It was isolated from ''[[Streptomyces noursei]]'' in 1950 by [[Elizabeth Lee Hazen]] and [[Rachel Fuller Brown]], who were doing research for the Division of Laboratories and Research of the New York State Department of Health. Hazen found a promising micro-organism in the soil of a friend's dairy farm. She named it ''Streptomyces noursei'', after Jessie Nourse, the wife of the farm's owner.<ref>{{cite book | vauthors = Espinel-Ingroff A | title = Medical mycology in the United States: a historical analysis (1894-1996) | publisher = Springer | date = 2003 | page = 62 }}</ref> Hazen and Brown named nystatin after the [[New York (state)|New York]] State Health Department in 1954.<ref name="Kelly">{{cite book | vauthors = Kelly K | title=Medicine Becomes a Science: 1840-1999 | year=2010 | isbn=978-1-4381-2752-1 | url=https://books.google.com/books?id=3L7_b_wrBXAC&pg=PA71 | page=71 | publisher=Infobase | url-status=live | archive-url=https://web.archive.org/web/20170323152325/https://books.google.com/books?id=3L7_b_wrBXAC&pg=PA71 | archive-date=23 March 2017 }}</ref> The two discoverers patented the drug, and then donated the $13 million in profits to a foundation to fund similar research.<ref name="Sicherman">{{cite book | vauthors = Sicherman B, Green CH | title=Notable American Women: The Modern Period : a Biographical Dictionary | publisher=Belknap Press of Harvard University Press | year=1980 | isbn=978-0-674-62733-8 | url=https://books.google.com/books?id=CfGHM9KU7aEC&pg=PA327 | page=327 | url-status=live | archive-url=https://web.archive.org/web/20170323163247/https://books.google.com/books?id=CfGHM9KU7aEC&pg=PA327 | archive-date=23 March 2017 }}</ref>

== Other uses ==

[[Image:Nystatin Mildew1c.jpg|thumb|''[[Penicillium]]''-infected tangerine: The spot absent of growth had nystatin applied to it before the [[fungus]] covered the fruit.]]

It is also used in cellular biology as an inhibitor of the [[lipid raft]]-[[caveolae]] [[Endocytosis|endocytosis pathway]] on mammalian cells, at concentrations around 3&nbsp;μg/ml.{{citation needed|date=December 2022}}

In certain cases, a nystatin derivative has been used to prevent the spread of mold on objects such as works of art. For example, it was applied to wood panel paintings damaged as a result of [[The Flood of the River Arno in Florence, Italy|the Arno River Flood of 1966 in Florence, Italy]].<ref>{{Cite journal | vauthors = Brommelle NS |date=1970 |title=The Restoration of Damaged Art Treasures in Florence and Venice |url=https://www.jstor.org/stable/41370578 |journal=Journal of the Royal Society of Arts |volume=118 |issue=5165 |pages=260–269 |jstor=41370578 |issn=0035-9114}}</ref>

Nystatin is also used as a tool by scientists performing [[Patch clamp#Perforated patch|"perforated" patch-clamp]] electrophysiological recordings of cells. When loaded in the recording pipette, it allows for measurement of electrical currents without washing out the intracellular contents, because it forms pores in the cell membrane that are permeable to only [[Monovalent ion|monovalent]] [[ions]],<ref name="pmid7534361">{{cite journal | vauthors = Akaike N, Harata N | title = Nystatin perforated patch recording and its applications to analyses of intracellular mechanisms | journal = The Japanese Journal of Physiology | volume = 44 | issue = 5 | pages = 433–473 | date = 1994 | pmid = 7534361 | doi = 10.2170/jjphysiol.44.433 | doi-access = free }}</ref> preferably cations such as sodium, potassium, lithium, and cesium.<ref>{{Citation | vauthors= Korn SJ, Marty A, Connor JA, Horn R |title=[22] - Perforated Patch Recording |date=1 January 1991 |url=https://www.sciencedirect.com/science/article/pii/B9780121852573500276 |work=Methods in Neurosciences |volume=4 |pages=364–373 | veditors = Conn PM |access-date=9 December 2023 |series=Electrophysiology and Microinjection |publisher=Academic Press |doi=10.1016/B978-0-12-185257-3.50027-6 |isbn=9780121852573 }}</ref>

[[File:Fusion Event via Current Measurement Large.jpg|thumb|This is a depiction of what a fusion event may look like when seen on a current measurement. There is a sudden jump in the current, followed by a slower recover as the current returns to its baseline measurement from before the fusion event. This fusion event would interrupt the stability of a nystatin pore.]]

Another electrophysiological measurement that can be made is fusion event duration in a nystatin-ergosterol based system. Fusions are measured while the voltage is held constant, and is characterized by a spike in the current that then returns to the baseline current as the nystatin channels close. When present in smaller concentrations, nystatin momentarily forms pores that allows a vesicle fusion to occur more easily; that fusion then interrupts the pore stability and the nystatin and ergosterol disperse from each other.<ref>{{Citation | vauthors = Rognlien KT, Woodbury DJ |title=Chapter 16 - Reconstituting SNARE proteins into BLMs |date=1 January 2003 |url=https://www.sciencedirect.com/science/article/pii/S0927519303800402 |work=Membrane Science and Technology |volume=7 |pages=479–488 | veditors = Tien HT, Ottova-Leitmannova A |access-date=9 December 2023 |series=Planar Lipid Bilayers (BLMs) and Their Applications |publisher=Elsevier |doi=10.1016/S0927-5193(03)80040-2 |isbn=9780444509406 }}</ref> Conversely, researchers have found that the half-life of these nystatin pores increase with an increased dosage level of nystatin to the membrane systems. This indicates a lower energy of both the lipid membrane and the ionophores when there is a higher concentration of nystatin.<ref>{{cite journal | vauthors = Coutinho A, Prieto M | title = Cooperative partition model of nystatin interaction with phospholipid vesicles | journal = Biophysical Journal | volume = 84 | issue = 5 | pages = 3061–3078 | date = May 2003 | pmid = 12719237 | pmc = 1302868 | doi = 10.1016/s0006-3495(03)70032-0 | bibcode = 2003BpJ....84.3061C }}</ref>

== Society and culture ==

=== Formulations ===

* An oral suspension form is used for the prophylaxis or treatment of oropharyngeal thrush, a superficial candidal infection of the mouth and pharynx.

* A tablet form is preferred for candidal infections in the intestines.

* Nystatin is available as a topical cream and can be used for superficial candidal infections of the skin.

* Additionally, a liposomal formulation of nystatin was investigated in the 1980s and into the early 21st century. The liposomal form was intended to resolve problems arising from the poor solubility of the parent molecule and the associated systemic toxicity of the free drug.

* Nystatin pastilles have been shown to be more effective in treating oral candidiasis than nystatin suspensions.<ref name=":0" />

Due to its [[toxicity]] profile when high levels in the serum are obtained, no injectable formulations of nystatin are on the US market. However, injectable formulations have been investigated in the past.<ref name="Dismukes 50–53">{{cite book| vauthors = Hamill RJ | chapter = Liposomal Nystatin | veditors = Dismukes WE, Pappas PG, Sobel JD |title=Clinical Mycology |year=2003 | chapter-url= https://archive.org/details/clinicalmycology00dism <!-- |url-access=limited --> |publisher=Oxford University Press |location=Oxford |isbn=978-0-19-514809-1 |pages=[https://archive.org/details/clinicalmycology00dism/page/n64 50]–53 }}</ref>

=== Brand names ===

{{div col|colwidth=20em}}

* Nyamyc

* Pedi-Dri

* Pediaderm AF Complete

* Candistatin

* Nyaderm

* Bio-Statin

* PMS-Nystatin

* Nystan (oral tablets, topical [[ointment]], and [[pessary|pessaries]], formerly from [[Bristol-Myers Squibb]])

* Infestat

* Nystalocal from Medinova AG

* Nystamont

* Nystop (topical powder, [[Paddock]])

* Nystex

* Mykinac

* Nysert (vaginal suppositories, [[Procter & Gamble]])

* Nystaform (topical cream, and ointment and cream combined with [[iodochlorhydroxyquine]] and [[hydrocortisone]]; formerly [[Bayer]] now [[Typharm]] Ltd)

* Nilstat (vaginal tablet, oral drops, [[Lederle Laboratories|Lederle]])

* Korostatin (vaginal tablets, [[Holland Rantos]])

* Mycostatin (vaginal tablets, topical powder, suspension [[Bristol-Myers Squibb]])

* Mycolog-II (topical ointment, combined with [[triamcinolone]]; [[Apothecon]])

* Mytrex (topical ointment, combined with triamcinolone)

* Mykacet (topical ointment, combined with triamcinolone)

* Myco-Triacet II (topical ointment, combined with triamcinolone)

* Flagystatin II (cream, combined with metronidazole)

* Timodine (cream, combined with [[hydrocortisone]] and [[dimethicone]])

* Nistatina (oral tablets, [[Antibiotice Iaşi]])

* Nidoflor (cream, combined with [[neomycin sulfate]] and [[triamcinolone acetonide]])

* Stamicin (oral tablets, [[Antibiotice Iaşi]])

* Lystin

* Animax (veterinary topical ointment or cream; combined with [[neomycin sulfate]], [[thiostrepton]] and [[triamcinolone acetonide]])

* Nyata (topical powder)<ref>{{Cite web|url=https://www.webmd.com/drugs/2/drug-172996/nyata-topical/details|title=Nyata 100,000 Unit/Gram Topical Powder - Uses, Side Effects, and More | publisher = WebMD LLC |access-date=11 November 2018}}</ref>

{{Div col end}}

== References ==

{{reflist}}

{{Portal bar | Medicine}}

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[[Category:Dermatoxins]]

[[Category:Wikipedia medicine articles ready to translate]]

[[Category:Polyketides]]

[[Category:Lactones]]

[[Category:Polyenes]]

[[Category:Hemiketals]]

[[Category:Lactols]]

[[Category:Lipid methods]]

[[Category:Vicinal diols]]

[[Category:Secondary alcohols]]

[[Category:Amines]]

[[Category:Carboxylic acids]]

[[Category:Conjugated dienes]]

[[Category:Acetals]]