# Topilutamide

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> Markdown URL: https://mediated.wiki/source/Topilutamide.md
> Source: https://en.wikipedia.org/wiki/Topilutamide
> Source revision: 1328694066
> License: Creative Commons Attribution-ShareAlike 4.0 International (https://creativecommons.org/licenses/by-sa/4.0/)

{{Short description|Chemical compound}}
{{Distinguish|Tolbutamide}}
{{Infobox drug
| Verifiedfields = 
| Watchedfields = 
| verifiedrevid = 
| IUPAC_name = 2-hydroxy-2-methyl-''N''-[4-nitro-3-(trifluoromethyl)phenyl]-3-[(2,2,2-trifluoroacetyl)amino]propanamide
| image = Topilutamide.svg
| image_class = skin-invert-image
| width = 250px

<!--Clinical data-->
| tradename = Eucapil
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_category = 
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| legal_CA = 
| legal_UK = 
| legal_US = 
| legal_status = 
| routes_of_administration = [Topical](/source/Topical)<ref name="pmid12174057" /><ref name="HaberStough2006" /><ref name="ScriptaMedica2006" /><ref name="AvramRogers2009" /><ref name="KirbyCarson2009" />
| class = [Nonsteroidal antiandrogen](/source/Nonsteroidal_antiandrogen)

<!--Pharmacokinetic data-->
| bioavailability = 
| protein_bound = 
| metabolism = 
| elimination_half-life = 
| excretion =

<!--Identifiers-->
| CAS_number_Ref = 
| CAS_number = 260980-89-0
| CAS_supplemental = 
| ATC_prefix = None
| ATC_suffix = 
| PubChem = 44147451
| DrugBank_Ref = 
| DrugBank = 
| ChemSpiderID_Ref = 
| ChemSpiderID = 8106619
| UNII = A8EU2FXY13
| synonyms = Fluridil; BP-766

<!--Chemical data-->
| C=13 | H=11 | F=6 | N=3 | O=5
| SMILES = C[C@@](CNC(=O)C(F)(F)F)(C(=O)NC1=CC(=C(C=C1)[N+](=O)[O-])C(F)(F)F)O
| StdInChI = 1S/C13H11F6N3O5/c1-11(25,5-20-10(24)13(17,18)19)9(23)21-6-2-3-8(22(26)27)7(4-6)12(14,15)16/h2-4,25H,5H2,1H3,(H,20,24)(H,21,23)/t11-/m1/s1
| StdInChIKey = YCNCRLKXSLARFT-LLVKDONJSA-N
}}

'''Topilutamide''', known more commonly as '''fluridil''' and sold under the brand name '''Eucapil''', is an [antiandrogen](/source/antiandrogen) medication which is used in the treatment of [pattern hair loss](/source/pattern_hair_loss) in men and women.<ref name="SeligsonCampion2003">{{cite journal| vauthors = Seligson AL, Campion BK, Brown JW, Terry RC, Kucerova R, Bienova M, Hajduch M, Sovak M |title=Development of fluridil, a topical suppressor of the androgen receptor in androgenetic alopecia|journal=Drug Development Research|volume=59|issue=3|year=2003|pages=292–306|issn=0272-4391|doi=10.1002/ddr.10166|s2cid=98640343|url=https://www.researchgate.net/publication/227651615}}</ref><ref name="pmid12174057">{{cite journal | vauthors = Sovak M, Seligson AL, Kucerova R, Bienova M, Hajduch M, Bucek M | title = Fluridil, a rationally designed topical agent for androgenetic alopecia: first clinical experience | journal = Dermatologic Surgery | volume = 28 | issue = 8 | pages = 678–85 | date = August 2002 | pmid = 12174057 | doi = 10.1046/j.1524-4725.2002.02017.x | s2cid = 36439600 }}</ref><ref name="HaberStough2006">{{cite book| vauthors = Haber RS, Stough DB |title=Hair Transplantation|url=https://books.google.com/books?id=PXJMqrbk-fAC&pg=PA7|year=2006|publisher=Elsevier Health Sciences|isbn=1-4160-3104-9|pages=7–}}</ref><ref name="ScriptaMedica2006">{{cite book|title=Scripta Medica|url=https://books.google.com/books?id=ynVRAQAAIAAJ|year=2006|pages=45, 53–54|quote=Fluridil was developed as a topical antiandrogen, suitable for the treatment of hyperandrogenic skin syndromes. The cosmetic product Eucapil® containing 2% fluridil in isopropanol was tested in women with AGA in a 9-month open study. [...] In a clinical study conducted at our facility, fluridil in solution (Eucapil®, Interpharma Praha, Czech Republic) has been shown to be effective and safe in the treatment of men with androgenetic alopecia (30, 31).}}</ref><ref name="AvramRogers2009">{{cite book| vauthors = Avram MR, Rogers NE |title=Hair Transplantation|url=https://books.google.com/books?id=j1XF1bnABFcC&pg=PA11|date=30 November 2009|publisher=Cambridge University Press|isbn=978-1-139-48339-1|pages=11–}}</ref><ref name="KirbyCarson2009">{{cite book|vauthors=Kirby RS, Carson CC, Kirby MG, White A|title=Men's Health, Third Edition|url=https://books.google.com/books?id=e-NyCQAAQBAJ&pg=PA362|date=29 January 2009|publisher=CRC Press|isbn=978-1-4398-0807-8|pages=362–}}</ref> It is used as a [topical medication](/source/topical_medication) and is applied to the [scalp](/source/scalp).<ref name="pmid12174057" /><ref name="HaberStough2006" /><ref name="ScriptaMedica2006" /><ref name="AvramRogers2009" /><ref name="KirbyCarson2009" /> Topilutamide belongs to a class of molecules known as perfluoroacylamido-arylpropanamides.<ref name="SeligsonCampion2003" />

Topilutamide is a [nonsteroidal antiandrogen](/source/nonsteroidal_antiandrogen) (NSAA), or an [antagonist](/source/receptor_antagonist) of the [androgen receptor](/source/androgen_receptor) (AR), the [biological target](/source/biological_target) of [androgen](/source/androgen)s like [testosterone](/source/testosterone) and [dihydrotestosterone](/source/dihydrotestosterone) (DHT).<ref name="pmid12174057" /><ref name="HaberStough2006" /><ref name="ScriptaMedica2006" /><ref name="AvramRogers2009" /><ref name="KirbyCarson2009" />

Topilutamide was introduced for medical use in 2003.<ref name="pmid16821162" /> It is marketed only in the [Czech Republic](/source/Czech_Republic) and [Slovakia](/source/Slovakia).<ref name="EucapilWebsite" /> The patent for Topilutamide expired in 2020.<ref name="SeligsonCampion2003" />

==Medical uses==
Topilutamide is used as a [topical medication](/source/topical_medication) in the treatment of [pattern hair loss](/source/pattern_hair_loss) in men and women.<ref name="pmid12174057" /><ref name="HaberStough2006" /><ref name="ScriptaMedica2006" /><ref name="AvramRogers2009" /><ref name="KirbyCarson2009" /> Topilutamide is approved for cosmetic use in Europe but has not received [FDA approval](/source/FDA_approval) nor approval by the [EMA](/source/European_Medicines_Agency) for the treatment of [androgenetic alopecia](/source/androgenetic_alopecia).<ref name="EucapilWebsite" /> [Finasteride](/source/Finasteride) and [Minoxidil](/source/Minoxidil) are currently the only treatments approved for the treatment of this condition.<ref name="HaberStough2006" />

===Available forms===
Under the brand name Eucapil, topilutamide is available as a 2% topical [formulation](/source/drug_formulation) intended for application to the [scalp](/source/scalp).<ref name="AvramRogers2009" />

==Pharmacology==

===Pharmacodynamics===
Topilutamide is an [antagonist](/source/receptor_antagonist) of the AR, the [biological target](/source/biological_target) of [androgen](/source/androgen)s like [testosterone](/source/testosterone) and DHT.<ref name="pmid12174057" /><ref name="HaberStough2006" /><ref name="ScriptaMedica2006" /><ref name="AvramRogers2009" /><ref name="KirbyCarson2009" /> Fluridil binds to the androgen receptor with approximately a 9-15-fold higher affinity than more primitive NSAAs such as [bicalutamide](/source/bicalutamide) and [hydroxyflutamide](/source/hydroxyflutamide), but more research is required to validate these findings.<ref name="SeligsonCampion2003" />
{| class="wikitable"
|+Percentage androgen receptor suppression in LNCaP Cells after 48-h Drug Incubation via Western Blot <ref name="SeligsonCampion2003" />
!Compound
!3 μM
!10 μM
|-
|BP-766 (Topilutamide)         
|41 ± 5           
|95.9 ± 6     
|-
|BP-521
|62 ± 7
|100
|-
|BP-34
|3 ± 4
|2 ± 2
|-
|Bicalutamide
|3 ± 3
|11 ± 3
|-
|Hydroxyflutamide
|2 ± 6
|6 ± 7
|}

=== Pharmacokinetics ===
Topilutamide is a [topical medication](/source/topical_medication) and is applied to the [scalp](/source/scalp).<ref name="pmid12174057" /><ref name="HaberStough2006" /><ref name="ScriptaMedica2006" /><ref name="AvramRogers2009" /><ref name="KirbyCarson2009" /> Topilutamide degrades in human serum at 37&nbsp;°C with a half-life of approximately 6 hours and is undetectable after 48 hours.<ref name="SeligsonCampion2003" /> Perfluoroacylamido-arylpropanamides decompose [hydrolytically](/source/Hydrolysis) to BP-34 and their corresponding [perfluorocarboxylic acid](/source/perfluorocarboxylic_acid).<ref name="SeligsonCampion2003" /> In the case of topilutamide, that perfluorocarboxylic acid is [trifluoroacetic acid](/source/trifluoroacetic_acid).<ref name="SeligsonCampion2003" /> The two metabolites of topilutamide namely BP-34 and trifluoroacetic acid were undetectable in human serum (below the detection limit of 5&nbsp;ng/mL) along with the parent compound topilutamide, in human studies.<ref name="SeligsonCampion2003" /> BP-34 was shown to be devoid of anti-androgenic activity.<ref name="SeligsonCampion2003" />

==Chemistry==
Topilutamide is a [nonsteroidal](/source/nonsteroidal) compound and is closely related to other NSAAs such as [flutamide](/source/flutamide) and [bicalutamide](/source/bicalutamide).<ref name="pmid16821162" />

==History==
Topilutamide was introduced for medical use in 2003.<ref name="pmid16821162">{{cite journal | vauthors = Hermkens PH, Kamp S, Lusher S, Veeneman GH | title = Non-steroidal steroid receptor modulators | journal = IDrugs | volume = 9 | issue = 7 | pages = 488–94 | date = July 2006 | pmid = 16821162 | doi = 10.2174/0929867053764671 }}</ref>

==Society and culture==

===Generic names===
''Topilutamide'' is the [generic name](/source/generic_term) of the drug and its {{abbrlink|INN|International Nonproprietary Name}}.<ref name="ChemIDplus">{{cite web|url=https://pubchem.ncbi.nlm.nih.gov/#tab/sidsrcname=ChemIDplus&query=260980-89-0&input_type=text|title=ChemIDplus - 260980-89-0 - YCNCRLKXSLARFT-UHFFFAOYSA-N - Topilutamide [INN] - Similar structures search, synonyms, formulas, resource links, and other chemical information. | vauthors = Chambers M |website=chem.nlm.nih.gov}}</ref><ref name="WHO2004">{{cite web|url=https://www.who.int/medicines/publications/druginformation/innlists/PL91.pdf |title=Microsoft Word - final_PL91.doc |access-date=2018-10-04}}</ref><ref name="Commission2008">{{cite book|author=United States International Trade Commission|title=Modifications to the Harmonized Tariff Schedule of the United States to Implement the Dominican Republic-Central America-United States Free Trade Agreement With Respect to Costa Rica|url=https://books.google.com/books?id=nun3ygnC0JoC&pg=PA18|year=2008|publisher=DIANE Publishing|isbn=978-1-4578-1723-6|pages=18–}}</ref> It is also known more commonly as ''fluridil''.<ref name="SeligsonCampion2003" /> Topilutamide is also known by its former developmental code name ''BP-766''.<ref name="SeligsonCampion2003" />

===Brand names===
Topilutamide is marketed by Interpharma Praha under the brand name Eucapil.<ref name="pmid16821162" /><ref name="ScriptaMedica2006" />

===Availability===
Topilutamide is available only in [Europe](/source/Europe) in the [Czech Republic](/source/Czech_Republic) and [Slovakia](/source/Slovakia).<ref name="EucapilWebsite">{{cite web|url=http://www.eucapil.com/xhtml_en/eucapil.shtml|title=Androgenetic Alopecia, Hair loss, Eucapil|website=www.eucapil.com}}</ref>

== See also ==
* [Clascoterone](/source/Clascoterone)
* [Pyrilutamide](/source/Pyrilutamide)
*[RU-58841](/source/RU-58841)
*[Finasteride](/source/Finasteride)
*[Dutasteride](/source/Dutasteride)
*[Minoxidil](/source/Minoxidil)

== References ==
{{Reflist}}

{{Androgens and antiandrogens}}
{{Other dermatological preparations}}
{{Androgen receptor modulators}}

Category:Acetamides
Category:Hair loss medications
Category:Nitrotoluene derivatives
Category:Nonsteroidal antiandrogens
Category:Propionamides
Category:Trifluoromethyl compounds

---
Adapted from the Wikipedia article [Topilutamide](https://en.wikipedia.org/wiki/Topilutamide) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Topilutamide?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.