Topilutamide

{{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

| 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 medication which is used in the treatment of 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 and is applied to the 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 (NSAA), or an antagonist of the androgen receptor (AR), the biological target of androgens like testosterone and 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 and Slovakia.<ref name="EucapilWebsite" /> The patent for Topilutamide expired in 2020.<ref name="SeligsonCampion2003" />

==Medical uses== Topilutamide is used as a topical medication in the treatment of 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 nor approval by the EMA for the treatment of androgenetic alopecia.<ref name="EucapilWebsite" /> Finasteride and 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 intended for application to the scalp.<ref name="AvramRogers2009" />

==Pharmacology==

===Pharmacodynamics=== Topilutamide is an antagonist of the AR, the biological target of androgens like 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 and 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 and is applied to the scalp.<ref name="pmid12174057" /><ref name="HaberStough2006" /><ref name="ScriptaMedica2006" /><ref name="AvramRogers2009" /><ref name="KirbyCarson2009" /> Topilutamide degrades in human serum at 37 °C with a half-life of approximately 6 hours and is undetectable after 48 hours.<ref name="SeligsonCampion2003" /> Perfluoroacylamido-arylpropanamides decompose hydrolytically to BP-34 and their corresponding perfluorocarboxylic acid.<ref name="SeligsonCampion2003" /> In the case of topilutamide, that perfluorocarboxylic acid is 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 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 compound and is closely related to other NSAAs such as flutamide and 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 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 in the Czech Republic and 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 * Pyrilutamide *RU-58841 *Finasteride *Dutasteride *Minoxidil

== References == {{Reflist}}

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