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{{Short description|Chemical compound}}
{{Distinguish|Tolbutamide}}
{{Distinguish|Tolbutamide}}
{{Drugbox
{{Drugbox
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'''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|author1=Robert S. Haber|author2=Dowling Bluford Stough|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|author1=Marc R. Avram|author2=Nicole E. Rogers|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''', 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 [[receptor antagonist|antagonist]] of the [[androgen receptor]] (AR), the [[biological target]] of [[androgen]]s like [[testosterone]] and [[dihydrotestosterone]] (DHT).<ref name="pmid12174057" /><ref name="HaberStough2006" /><ref name="ScriptaMedica2006" /><ref name="AvramRogers2009" /><ref name="KirbyCarson2009" />
Topilutamide is a [[nonsteroidal antiandrogen]] (NSAA), or an [[receptor antagonist|antagonist]] of the [[androgen receptor]] (AR), the [[biological target]] of [[androgen]]s like [[testosterone]] and [[dihydrotestosterone]] (DHT).<ref name="pmid12174057" /><ref name="HaberStough2006" /><ref name="ScriptaMedica2006" /><ref name="AvramRogers2009" /><ref name="KirbyCarson2009" />
Line 56: Line 57:


==Medical uses==
==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 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 [[European Medicines Agency|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===
===Available forms===
As Eucapil, topilutamide is available as a 2% topical [[drug formulation|formulation]] intended for application to the [[scalp]].<ref name="AvramRogers2009" />
Under the brand name Eucapil, topilutamide is available as a 2% topical [[drug formulation|formulation]] intended for application to the [[scalp]].<ref name="AvramRogers2009" />


==Pharmacology==
==Pharmacology==


===Pharmacodynamics===
===Pharmacodynamics===
Topilutamide is an [[receptor antagonist|antagonist]] of the AR, the [[biological target]] of [[androgen]]s 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 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" />
Topilutamide is an [[receptor antagonist|antagonist]] of the AR, the [[biological target]] of [[androgen]]s 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===
=== 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" /> Fluridil 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 [[Hydrolysis|hydrolytically]] to BP-34 and their corresponding [[perfluorocarboxylic acid]]. <ref name="SeligsonCampion2003" /> In the case of Topilutamide, that perfluorocarboxylic acid is [[Trifluoroacetic acid|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 5ng/mL) along with the parent compound Topilutamide, in human studies. <ref name="SeligsonCampion2003" />
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&nbsp;°C with a half-life of approximately 6 hours and is undetectable after 48 hours.<ref name="SeligsonCampion2003" /> Perfluoroacylamido-arylpropanamides decompose [[Hydrolysis|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&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==
==Chemistry==
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== See also ==
== See also ==
* [[Clascoterone]]
* [[Clascoterone]]
* [[Pyrilutamide]]
*[[RU-58841]]
*[[Finasteride]]
*[[Dutasteride]]
*[[Minoxidil]]


== References ==
== References ==
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[[Category:Acetamides]]
[[Category:Acetamides]]
[[Category:Hair loss medications]]
[[Category:Hair loss medications]]
[[Category:Nitrobenzenes]]
[[Category:Nitrotoluene derivatives]]
[[Category:Nonsteroidal antiandrogens]]
[[Category:Nonsteroidal antiandrogens]]
[[Category:Propionamides]]
[[Category:Propionamides]]

Latest revision as of 22:08, 3 February 2024

Not to be confused with Tolbutamide.
Topilutamide
Clinical data
Trade namesEucapil
Other namesFluridil; BP-766
Routes of
administration		Topical[1][2][3][4][5]
Drug classNonsteroidal antiandrogen
ATC code
  • None
Identifiers
  • 2-hydroxy-2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]-3-[(2,2,2-trifluoroacetyl)amino]propanamide
CAS Number
PubChem CID
ChemSpider
UNII
ECHA InfoCard100.245.367 Edit this at Wikidata
Chemical and physical data
FormulaC13H11F6N3O5
Molar mass403.237 g·mol−1
3D model (JSmol)
  • C[C@@](CNC(=O)C(F)(F)F)(C(=O)NC1=CC(=C(C=C1)[N+](=O)[O-])C(F)(F)F)O
  • InChI=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
  • Key: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.[6][1][2][3][4][5] It is used as a topical medication and is applied to the scalp.[1][2][3][4][5] Topilutamide belongs to a class of molecules known as perfluoroacylamido-arylpropanamides.[6]

Topilutamide is a nonsteroidal antiandrogen (NSAA), or an antagonist of the androgen receptor (AR), the biological target of androgens like testosterone and dihydrotestosterone (DHT).[1][2][3][4][5]

Topilutamide was introduced for medical use in 2003.[7] It is marketed only in the Czech Republic and Slovakia.[8] The patent for Topilutamide expired in 2020.[6]

Medical uses

[edit]

Topilutamide is used as a topical medication in the treatment of pattern hair loss in men and women.[1][2][3][4][5] 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.[8] Finasteride and Minoxidil are currently the only treatments approved for the treatment of this condition.[2]

Available forms

[edit]

Under the brand name Eucapil, topilutamide is available as a 2% topical formulation intended for application to the scalp.[4]

Pharmacology

[edit]

Pharmacodynamics

[edit]

Topilutamide is an antagonist of the AR, the biological target of androgens like testosterone and DHT.[1][2][3][4][5] 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.[6]

Percentage androgen receptor suppression in LNCaP Cells after 48-h Drug Incubation via Western Blot [6]
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

[edit]

Topilutamide is a topical medication and is applied to the scalp.[1][2][3][4][5] Topilutamide degrades in human serum at 37 °C with a half-life of approximately 6 hours and is undetectable after 48 hours.[6] Perfluoroacylamido-arylpropanamides decompose hydrolytically to BP-34 and their corresponding perfluorocarboxylic acid.[6] In the case of topilutamide, that perfluorocarboxylic acid is trifluoroacetic acid.[6] 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.[6] BP-34 was shown to be devoid of anti-androgenic activity.[6]

Chemistry

[edit]

Topilutamide is a nonsteroidal compound and is closely related to other NSAAs such as flutamide and bicalutamide.[7]

History

[edit]

Topilutamide was introduced for medical use in 2003.[7]

Society and culture

[edit]

Generic names

[edit]

Topilutamide is the generic name of the drug and its INNTooltip International Nonproprietary Name.[9][10][11] It is also known more commonly as fluridil.[6] Topilutamide is also known by its former developmental code name BP-766.[6]

Brand names

[edit]

Topilutamide is marketed by Interpharma Praha under the brand name Eucapil.[7][3]

Availability

[edit]

Topilutamide is available only in Europe in the Czech Republic and Slovakia.[8]

See also

[edit]

References

[edit]
  1. ^ a b c d e f g Sovak M, Seligson AL, Kucerova R, Bienova M, Hajduch M, Bucek M (August 2002). "Fluridil, a rationally designed topical agent for androgenetic alopecia: first clinical experience". Dermatologic Surgery. 28 (8): 678–85. doi:10.1046/j.1524-4725.2002.02017.x. PMID 12174057. S2CID 36439600.
  2. ^ a b c d e f g h Haber RS, Stough DB (2006). Hair Transplantation. Elsevier Health Sciences. pp. 7–. ISBN 1-4160-3104-9.
  3. ^ a b c d e f g h Scripta Medica. 2006. pp. 45, 53–54. 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).
  4. ^ a b c d e f g h Avram MR, Rogers NE (30 November 2009). Hair Transplantation. Cambridge University Press. pp. 11–. ISBN 978-1-139-48339-1.
  5. ^ a b c d e f g Kirby RS, Carson CC, Kirby MG, White A (29 January 2009). Men's Health, Third Edition. CRC Press. pp. 362–. ISBN 978-1-4398-0807-8.
  6. ^ a b c d e f g h i j k l Seligson AL, Campion BK, Brown JW, Terry RC, Kucerova R, Bienova M, Hajduch M, Sovak M (2003). "Development of fluridil, a topical suppressor of the androgen receptor in androgenetic alopecia". Drug Development Research. 59 (3): 292–306. doi:10.1002/ddr.10166. ISSN 0272-4391. S2CID 98640343.
  7. ^ a b c d Hermkens PH, Kamp S, Lusher S, Veeneman GH (July 2006). "Non-steroidal steroid receptor modulators". IDrugs. 9 (7): 488–94. doi:10.2174/0929867053764671. PMID 16821162.
  8. ^ a b c "Androgenetic Alopecia,Hair loss,Eucapil". www.eucapil.com.
  9. ^ Chambers M. "ChemIDplus - 260980-89-0 - YCNCRLKXSLARFT-UHFFFAOYSA-N - Topilutamide [INN] - Similar structures search, synonyms, formulas, resource links, and other chemical information". chem.nlm.nih.gov.
  10. ^ "Microsoft Word - final_PL91.doc" (PDF). Retrieved 2018-10-04.
  11. ^ United States International Trade Commission (2008). 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. DIANE Publishing. pp. 18–. ISBN 978-1-4578-1723-6.
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