Anidulafungin: Difference between revisions

{{short description|Antifungal medication}}

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

| verifiedrevid = 457130635

| IUPAC_name = ''N''-[(3''S'',6''S'',9''S'',11''R'',15''S'',18''S'',20''R'',21''R'',24''S'',25''S'',26''S'')-6-[(1''S'',2''R'')-1,2-Dihydroxy-2-(4-hydroxyphenyl)ethyl]-11,20,21,25-tetrahydroxy-3,15-''bis''[(1''R'')-1-hydroxyethyl]-26-methyl-2,5,8,14,17,23-hexaoxo-1,4,7,13,16,22-hexaazatricyclo[22.3.0.0^9,13]heptacosan-18-yl]- 4-<nowiki/>{4-[4-(pentyloxy)phenyl]phenyl}benzamide

| image = Anidulafungin structure.svg

| width = 300

| pronounce = {{IPAc-en|eɪ|ˌ|n|ɪ|dj|ʊ|l|ə|ˈ|f|ʌ|n|dʒ|ɪ|n}} {{respell|ay|NID|yuu|lə|FUN|jin}}

| tradename = Eraxis, Ecalta

| licence_EU = yes

| licence_US = Anidulafungin

| pregnancy_US = B

| legal_status = Rx-only

| routes_of_administration = [[Intravenous therapy|Intravenous]]

| bioavailability = 100% (intravenous use only)

| protein_bound = Extensive (>99%)

| metabolism = [[Liver|Hepatic]] metabolism not observed, [[Cytochrome P450|CYP]] system not involved

| elimination_half-life = 27 hours; 40–50 hours (terminal)

| excretion = [[Feces]] (~30%), [[urine]] (<1%)

| CAS_number_Ref = {{cascite|correct|??}}

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

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

| KEGG = D03211

| ChEBI_Ref = {{ebicite|changed|EBI}}

| ChEBI = 55346

| ChEMBL = 1630215

| synonyms = <small>(4''R'',5''S'')-4,5-Dihydroxy-''N''²-<nowiki>[[</nowiki>4<nowiki>''</nowiki>-(pentyloxy)-''p''-terphenyl-4-yl]carbonyl]-<small>L</small>-ornithyl-<small>L</small>-threonyl-''trans''-4-hydroxy-<small>L</small>-prolyl-(''S'')-4-hydroxy-4-(''p''-hydroxyphenyl)-<small>L</small>-threonyl-<small>L</small>-threonyl-(3''S'',4''S'')-3-hydroxy-4-methyl-<small>L</small>-proline cyclic (6→1)-peptide<ref name="INN">{{cite web|title=International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary names: List 43|url=https://www.who.int/medicines/publications/druginformation/innlists/RL43.pdf|publisher=World Health Organization|access-date=11 November 2016|date=2000}}</ref><br />1-[(4''R'',5''R'')-4,5-Dihydroxy-''N''²-<nowiki>[[</nowiki>4<nowiki>''</nowiki>-(pentyloxy)[1',1':4',1<nowiki>''</nowiki>-terphenyl]-4-yl]carbonyl]-<small>L</small>-ornithine]echinocandin B<ref name="PI">{{cite web|title=Eraxis (anidulafungin) for Injection, for Intravenous Use. Full Prescribing Information|url=http://labeling.pfizer.com/ShowLabeling.aspx?id=566#section-8.1|publisher=Roerig (Division of Pfizer, Inc.), New York, NY 10017|access-date=11 November 2016}}</ref></small>

<!--Chemical data-->

| C=58 | H=73 | N=7 | O=17

| SMILES = CCCCCOc1ccc(cc1)c2ccc(cc2)c3ccc(cc3)C(=O)N[C@H]6C[C@@H](O)[C@@H](O)NC(=O)C4[C@@H](O)[C@@H](C)CN4C(=O)C(NC(=O)C(NC(=O)C5C[C@@H](O)CN5C(=O)C(NC6=O)[C@@H](C)O)[C@@H](O)[C@H](O)c7ccc(O)cc7)[C@@H](C)O

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

'''Anidulafungin''' ([[International nonproprietary name|INN]])<ref name="INN" />{{rp|42}} (trade names '''Eraxis''', '''Ecalta''') is a [[Semisynthesis|semisynthetic]] [[echinocandin]] used as an [[antifungal medication|antifungal drug]]. It was previously known as LY303366.<ref>{{cite journal | vauthors = Krause DS, Reinhardt J, Vazquez JA, Reboli A, Goldstein BP, Wible M, Henkel T | title = Phase 2, randomized, dose-ranging study evaluating the safety and efficacy of anidulafungin in invasive candidiasis and candidemia | journal = Antimicrobial Agents and Chemotherapy | volume = 48 | issue = 6 | pages = 2021–2024 | date = June 2004 | pmid = 15155194 | pmc = 415613 | doi = 10.1128/AAC.48.6.2021-2024.2004 }}</ref><ref>{{cite journal | vauthors = Pfaller MA, Boyken L, Hollis RJ, Messer SA, Tendolkar S, Diekema DJ | title = In vitro activities of anidulafungin against more than 2,500 clinical isolates of Candida spp., including 315 isolates resistant to fluconazole | journal = Journal of Clinical Microbiology | volume = 43 | issue = 11 | pages = 5425–5427 | date = November 2005 | pmid = 16272464 | pmc = 1287823 | doi = 10.1128/JCM.43.11.5425-5427.2005 }}</ref><ref>{{cite journal | vauthors = Pfaller MA, Diekema DJ, Boyken L, Messer SA, Tendolkar S, Hollis RJ, Goldstein BP | title = Effectiveness of anidulafungin in eradicating Candida species in invasive candidiasis | journal = Antimicrobial Agents and Chemotherapy | volume = 49 | issue = 11 | pages = 4795–4797 | date = November 2005 | pmid = 16251335 | pmc = 1280139 | doi = 10.1128/AAC.49.11.4795-4797.2005 }}</ref> It may also have application in treating invasive ''[[Aspergillus]]'' infection when used in combination with [[voriconazole]].<ref>{{cite journal | vauthors = Grau S, Azanza JR, Ruiz I, Vallejo C, Mensa J, Maertens J, Heinz WJ, Barrueta JA, Peral C, Mesa FJ, Barrado M, Charbonneau C, Rubio-Rodríguez D, Rubio-Terrés C | title = Cost-effectiveness analysis of combination antifungal therapy with voriconazole and anidulafungin versus voriconazole monotherapy for primary treatment of invasive aspergillosis in Spain | journal = ClinicoEconomics and Outcomes Research | volume = 9 | pages = 39–47 | date = January 2017 | pmid = 28115858 | pmc = 5221484 | doi = 10.2147/CEOR.S122177 | doi-access = free }}</ref> It is a member of the class of antifungal drugs known as the [[echinocandin]]s; its mechanism of action is by inhibition of [[Beta-glucan|(1→3)-β-<small>D</small>-glucan]] synthase, an enzyme important to the synthesis of the fungal cell wall.<ref>{{cite journal | vauthors = Zida A, Bamba S, Yacouba A, Ouedraogo-Traore R, Guiguemdé RT | title = Anti-Candida albicans natural products, sources of new antifungal drugs: A review | journal = Journal de Mycologie Médicale | volume = 27 | issue = 1 | pages = 1–19 | date = March 2017 | pmid = 27842800 | doi = 10.1016/j.mycmed.2016.10.002 }}</ref>

It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO22nd">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 22nd list (2021) | year = 2021 | hdl = 10665/345533 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2021.02 | hdl-access=free }}</ref>

==Indications==

* [[Fungemia|Candidemia]] and other forms of invasive ''Candida'' infections (intra-abdominal [[abscess]] and [[peritonitis]])

* [[Esophageal candidiasis]]

Anidulafungin has not been studied in [[Infective endocarditis#Fungal|endocarditis]], [[osteomyelitis]], and [[Meningitis#Fungal|meningitis]] due to ''Candida'', and has not been studied in sufficient numbers of [[Neutropenia|neutropenic]] patients to determine efficacy in this group.<ref name="PI" />

==Pharmacology==

==Pharmacodynamics==

Anidulafungin significantly differs from other antifungals in that it undergoes chemical degradation to inactive forms at body [[pH]] and temperature. Because it does not rely on enzymatic degradation or hepatic or renal excretion, the drug is safe to use in patients with any degree of hepatic or renal impairment.<ref>{{cite web|title=Eraxis | work = RxList|url=http://www.rxlist.com/eraxis-drug.htm#cp|date= 24 June 2009 |access-date= 1 August 2009}}</ref>

{| {{table}}

! Parameter

! Value

|-

| [[Volume of distribution]] (L)

| 30–50 L.<ref name="Kofla_2011">{{cite journal | vauthors = Kofla G, Ruhnke M | title = Pharmacology and metabolism of anidulafungin, caspofungin and micafungin in the treatment of invasive candidosis: review of the literature | journal = European Journal of Medical Research | volume = 16 | issue = 4 | pages = 159–166 | date = April 2011 | pmid = 21486730 | pmc = 3352072 | doi = 10.1186/2047-783x-16-4-159 | doi-access = free }}</ref>

|-

| [[Plasma protein binding]] (%)

| 99%<ref name="Kofla_2011" />

|-

| [[Elimination half-life]] [h]

| 24 hours<ref name="Kofla_2011" />

|}

==Pharmacokinetics==

Anidulafungin is not evidently metabolized by the [[liver]]. This specific drug undergoes slow chemical [[hydrolysis]] to an open-ring peptide which lacks antifungal activity. The half-life of the drug is 27 hours. About 30% is excreted in the feces (10% as unchanged drug). Less than 1% is excreted in the urine.<ref name="pmid15821277">{{cite journal | vauthors = Trissel LA, Ogundele AB | title = Compatibility of anidulafungin with other drugs during simulated Y-site administration | journal = American Journal of Health-System Pharmacy | volume = 62 | issue = 8 | pages = 834–837 | date = April 2005 | pmid = 15821277 | doi = 10.1093/ajhp/62.8.834 | doi-access = free }}</ref><ref name="pmid16117974">{{cite journal | vauthors = Vazquez JA | title = Anidulafungin: a new echinocandin with a novel profile | journal = Clinical Therapeutics | volume = 27 | issue = 6 | pages = 657–673 | date = June 2005 | pmid = 16117974 | doi = 10.1016/j.clinthera.2005.06.010 }}</ref><ref name="pmid18177225">{{cite journal | vauthors = Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, Morrison VA, Segal BH, Steinbach WJ, Stevens DA, van Burik JA, Wingard JR, Patterson TF | title = Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America | journal = Clinical Infectious Diseases | volume = 46 | issue = 3 | pages = 327–360 | date = February 2008 | pmid = 18177225 | doi = 10.1086/525258 | s2cid = 8789905 | url = https://pure.manchester.ac.uk/ws/files/23880159/POST-PEER-REVIEW-PUBLISHERS-DOCUMENT.PDF }}</ref>

Anidulafungin inhibits [[Cellulose synthase (UDP-forming)|glucan synthase]], an enzyme important in the formation of (1→3)-β-<small>D</small>-glucan, a major fungal cell wall component. Glucan synthase is not present in mammalian cells, so it is an attractive target for antifungal activity.<ref name=pmid9421307>{{cite journal | vauthors = Denning DW | title = Echinocandins and pneumocandins--a new antifungal class with a novel mode of action | journal = The Journal of Antimicrobial Chemotherapy | volume = 40 | issue = 5 | pages = 611–614 | date = November 1997 | pmid = 9421307 | doi = 10.1093/jac/dkf045 | doi-access = free }}</ref>

==Semisynthesis==

Anidulafungin is manufactured via semi-synthesis. The starting material is [[echinocandin B]] (a [[lipopeptide]] fermentation product of ''[[Aspergillus nidulans]]'' or the closely related species, ''A. rugulosus''), which undergoes deacylation (cleavage of the [[lenoleic acid|linoleoyl]] side chain) by the action of a deacylase enzyme from the bacterium ''[[Actinoplanes utahensis]]'';<ref>{{cite journal | vauthors = Shao L, Li J, Liu A, Chang Q, Lin H, Chen D | title = Efficient bioconversion of echinocandin B to its nucleus by overexpression of deacylase genes in different host strains | journal = Applied and Environmental Microbiology | volume = 79 | issue = 4 | pages = 1126–1133 | date = February 2013 | pmid = 23220968 | pmc = 3568618 | doi = 10.1128/AEM.02792-12 | bibcode = 2013ApEnM..79.1126S }}</ref> in three subsequent synthetic steps, including a chemical reacylation, the antifungal drug anidulafungin<ref name=pmid9421307 /><ref name="urlAnidulafungin">{{cite web |url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000788/WC500020676.pdf|title = Anidulafungin | work = EMA Europa | date = 2007 }}</ref> is synthesized.

==History==

Anidulafungin was originally discovered at Lilly laboratories by Turner and Debono and licensed to Vicuron Pharmaceuticals who submitted it to the FDA.<ref>{{cite web | work = PRNewswire | url = http://www2.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=/www/story/08-18-2005/0004090960&EDATE= | title = Vicuron Pharmaceuticals Files New Drug Application (NDA) for Anidulafungin for Treatment of Invasive Candidiasis/Candidemia | archive-url = https://web.archive.org/web/20120516004149/http://www2.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=%2Fwww%2Fstory%2F08-18-2005%2F0004090960&EDATE= | archive-date= 16 May 2012| date = 18 August 2005 }}</ref> [[Pfizer]] acquired the drug upon its acquisition of Vicuron in the fall of 2005.<ref>{{cite web | work = PRNewswire | url = http://www2.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=/www/story/08-15-2005/0004088704&EDATE= | title = Vicuron Pharmaceuticals Stockholders Approve Merger With Pfizer | archive-url = https://web.archive.org/web/20120516004221/http://www2.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=%2Fwww%2Fstory%2F08-15-2005%2F0004088704&EDATE= | archive-date = 16 May 2012 | date = 15 August 2005 }}</ref> Pfizer gained approval by the [[Food and Drug Administration]] (FDA) on February 21, 2006.<ref>{{cite web|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2006/ucm108602.htm|title=FDA Approves New Treatment for Fungal Infections|date=2006-02-21|work=FDA News Release|publisher=[[Food and Drug Administration (United States)|Food and Drug Administration]]|access-date= 1 August 2009 | archive-url= https://web.archive.org/web/20090710031821/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2006/ucm108602.htm| archive-date= 10 July 2009 | url-status= live}}</ref>

== References ==

{{Reflist}}

{{Antifungals}}

[[Category:Antifungals]]

[[Category:Echinocandins]]

[[Category:Drugs developed by Pfizer]]

[[Category:World Health Organization essential medicines]]

[[Category:Pentyl compounds]]