Editing Amphotericin B (section)

== Available formulations ==

=== Intravenous ===
Amphotericin B alone is [[Solubility|insoluble]] in [[Saline (medicine)|normal saline]] at a [[pH]] of 7. Therefore, several formulations have been devised to improve its intravenous bioavailability.<ref name="Dutcher_1968" /> Lipid-based formulations of amphotericin B are no more effective than conventional formulations, although some evidence suggests lipid-based formulations may be better tolerated and have fewer adverse effects.<ref>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.</ref>

==== Deoxycholate ====
The original formulation uses sodium [[Deoxycholic acid|deoxycholate]] to improve solubility.<ref name="Hamill_2013"/> Amphotericin B deoxycholate (ABD) is administered [[Intravenous therapy|intravenously]].<ref name="Maertens_2004" /> As the original formulation of amphotericin, it is often referred to as "conventional" amphotericin.<ref>{{cite journal | vauthors = Clemons KV, Stevens DA | title = Comparison of fungizone, Amphotec, AmBisome, and Abelcet for treatment of systemic murine cryptococcosis | journal = Antimicrobial Agents and Chemotherapy | volume = 42 | issue = 4 | pages = 899–902 | date = April 1998 | pmid = 9559804 | pmc = 105563 | doi = 10.1128/AAC.42.4.899 }}</ref>

==== Liposomal ====
To improve the tolerability of amphotericin and reduce toxicity, researchers developed several lipid formulations.<ref name="Hamill_2013" /> Liposomal formulations have been found to have less renal toxicity than deoxycholate,<ref>{{cite journal | vauthors = Botero Aguirre JP, Restrepo Hamid AM | title = Amphotericin B deoxycholate versus liposomal amphotericin B: effects on kidney function | journal = The Cochrane Database of Systematic Reviews | issue = 11 | pages = CD010481 | date = November 2015 | volume = 2015 | pmid = 26595825 | doi = 10.1002/14651858.cd010481.pub2 | doi-access = free | pmc = 10542271 }}</ref><ref>{{cite journal | vauthors = Mistro S, Maciel I, de Menezes RG, Maia ZP, Schooley RT, Badaró R | title = Does lipid emulsion reduce amphotericin B nephrotoxicity? A systematic review and meta-analysis | journal = Clinical Infectious Diseases | volume = 54 | issue = 12 | pages = 1774–1777 | date = June 2012 | pmid = 22491505 | doi = 10.1093/cid/cis290 | doi-access = free }}</ref> and fewer infusion-related reactions.<ref name="Hamill_2013" /> They are more expensive than amphotericin B deoxycholate.<ref>{{cite journal | vauthors = Bennett J | title = Editorial response: choosing amphotericin B formulations-between a rock and a hard place | journal = Clinical Infectious Diseases | volume = 31 | issue = 5 | pages = 1164–1165 | date = November 2000 | pmid = 11073746 | doi = 10.1086/317443 | doi-access = free }}</ref>

AmBisome (liposomal amphotericin B; LAMB) is a liposomal formulation of amphotericin B for [[Injection (medicine)|injection]] and consists of a mixture of [[phosphatidylcholine]], [[cholesterol]] and distearoyl phosphatidylglycerol that in aqueous media spontaneously arrange into [[Unilamellar liposome|unilamellar vesicles]] that contain amphotericin B.<ref name="Hamill_2013" /><ref name="Slain_1999">{{cite journal | vauthors = Slain D | title = Lipid-based amphotericin B for the treatment of fungal infections | journal = Pharmacotherapy | volume = 19 | issue = 3 | pages = 306–323 | date = March 1999 | pmid = 10221369 | doi = 10.1592/phco.19.4.306.30934 | s2cid = 43479677 }}</ref> It was developed by NeXstar Pharmaceuticals (acquired by [[Gilead Sciences]] in 1999). It was approved by the FDA in 1997.<ref>{{cite web|url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/050740_ambisome_toc.cfm|title=Drug Approval Package|website=www.accessdata.fda.gov|access-date=2015-11-03|url-status=live|archive-url=https://web.archive.org/web/20151117033232/http://www.accessdata.fda.gov/drugsatfda_docs/nda/97/050740_ambisome_toc.cfm|archive-date=2015-11-17}}</ref> It is marketed by Gilead in Europe and licensed to [[Astellas Pharma]] (formerly Fujisawa Pharmaceuticals) for marketing in the US, and [[Sumitomo Chemical|Sumitomo Pharmaceuticals]] in Japan.{{citation needed|date=June 2022}}

==== Lipid complex formulations ====
Several lipid complex preparations are also available. Abelcet was approved by the [[Food and Drug Administration|FDA]] in 1995.<ref name="accessdata.fda.gov">{{cite web|title = Drugs@FDA: FDA Approved Drug Products|url = http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails|website = www.accessdata.fda.gov|access-date = 2015-11-03|url-status = dead|archive-url = https://web.archive.org/web/20140813131107/http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails|archive-date = 2014-08-13}}</ref> It consists of amphotericin B and two lipids in a 1:1 ratio that form large ribbon-like structures.<ref name="Hamill_2013" /> Amphotec is a complex of amphotericin and sodium cholesteryl sulfate in a 1:1 ratio. Two molecules of each form a tetramer that aggregates into spiral arms on a disk-like complex.<ref name="Slain_1999" /> It was approved by the FDA in 1996.<ref name="accessdata.fda.gov"/>

===By mouth===
An oral preparation exists but is not widely available.<ref>{{cite journal | vauthors = Wasan KM, Wasan EK, Gershkovich P, Zhu X, Tidwell RR, Werbovetz KA, Clement JG, Thornton SJ | title = Highly effective oral amphotericin B formulation against murine visceral leishmaniasis | journal = The Journal of Infectious Diseases | volume = 200 | issue = 3 | pages = 357–360 | date = August 2009 | pmid = 19545212 | doi = 10.1086/600105 | doi-access =  }}</ref> 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 [[Candidiasis|thrush]], but has been replaced by other antifungals such as [[nystatin]] and [[fluconazole]].<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>

However, recently novel nanoparticulate drug delivery systems such as AmbiOnp,<ref name="AmbiOnp: solid lipid nanoparticles">{{cite journal | vauthors = Patel PA, Patravale VB | title = AmbiOnp: solid lipid nanoparticles of amphotericin B for oral administration | journal = Journal of Biomedical Nanotechnology | volume = 7 | issue = 5 | pages = 632–639 | date = October 2011 | pmid = 22195480 | doi = 10.1166/jbn.2011.1332 }}</ref> nanosuspensions, lipid-based drug delivery systems including cochleates, self-emulsifying drug delivery systems,<ref>{{cite journal | vauthors = Wasan EK, Bartlett K, Gershkovich P, Sivak O, Banno B, Wong Z, Gagnon J, Gates B, Leon CG, Wasan KM | title = 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 | journal = International Journal of Pharmaceutics | volume = 372 | issue = 1–2 | pages = 76–84 | date = May 2009 | pmid = 19236839 | doi = 10.1016/j.ijpharm.2009.01.003 }}</ref> solid lipid [[nanoparticle]]s<ref name="AmbiOnp: solid lipid nanoparticles"/> and polymeric nanoparticles<ref>{{cite journal | vauthors = Italia JL, Yahya MM, Singh D, Ravi Kumar MN | title = Biodegradable nanoparticles improve oral bioavailability of amphotericin B and show reduced nephrotoxicity compared to intravenous Fungizone | journal = Pharmaceutical Research | volume = 26 | issue = 6 | pages = 1324–1331 | date = June 2009 | pmid = 19214716 | doi = 10.1007/s11095-009-9841-2 | s2cid = 8612917 }}</ref>—such as amphotericin B in pegylated polylactide coglycolide copolymer nanoparticles<ref>{{cite journal | vauthors = Al-Quadeib BT, Radwan MA, Siller L, Horrocks B, Wright MC | title = Stealth Amphotericin B nanoparticles for oral drug delivery: In vitro optimization | journal = Saudi Pharmaceutical Journal | volume = 23 | issue = 3 | pages = 290–302 | date = July 2015 | pmid = 26106277 | pmc = 4475820 | doi = 10.1016/j.jsps.2014.11.004 }}</ref>—have demonstrated potential for oral formulation of amphotericin B.<ref>{{cite journal | vauthors = Patel PA, Fernandes CB, Pol AS, Patravale VB | title = Oral amphotericin B: challenges and avenues. | journal = Int. J. Pharm. Biosci. Technol. | date = 2013 | volume = 1 | issue = 1 | pages = 1–9 | url = https://www.researchgate.net/publication/236578662 }}</ref> The oral lipid nanocrystal amphotericin by Matinas Biopharma is furthest along, having completed a successful phase 2 clinical trial in cryptococcal meningitis.<ref>{{cite journal | vauthors = Boulware DR, Atukunda M, Kagimu E, Musubire AK, Akampurira A, Tugume L, Ssebambulidde K, Kasibante J, Nsangi L, Mugabi T, Gakuru J, Kimuda S, Kasozi D, Namombwe S, Turyasingura I, Rutakingirwa MK, Mpoza E, Kigozi E, Muzoora C, Ellis J, Skipper CP, Matkovits T, Williamson PR, Williams DA, Fieberg A, Hullsiek KH, Abassi M, Dai B, Meya DB | title = Oral Lipid Nanocrystal Amphotericin B for Cryptococcal Meningitis: A Randomized Clinical Trial | journal = Clinical Infectious Diseases | date = August 2023 | volume = 77 | issue = 12 | pages = 1659–1667 | pmid = 37606364 | doi = 10.1093/cid/ciad440 | doi-access = free | pmc = 10724459 }}</ref>