Topilutamide

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
Clinical data
Trade namesEucapil
Other namesFluridil; BP-766
Routes of
administration
Topical[1][2][3][4][5]
Drug classNonsteroidal antiandrogen
ATC code
  • None
Identifiers
IUPAC name
  • 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
Chemical and physical data
FormulaC13H11F6N3O5
Molar mass403.237 g·mol−1
3D model (JSmol)
SMILES
  • C[C@@](CNC(=O)C(F)(F)F)(C(=O)NC1=CC(=C(C=C1)[N+](=O)[O-])C(F)(F)F)O
InChI
  • 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 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

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

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

Pharmacology

Pharmacodynamics

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

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

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

History

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

Society and culture

Generic names

Topilutamide is the generic name of the drug and its INN.[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

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

Availability

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

See also

References

  1. 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. Haber RS, Stough DB (2006). Hair Transplantation. Elsevier Health Sciences. pp. 7–. ISBN 1-4160-3104-9.
  3. 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. Avram MR, Rogers NE (30 November 2009). Hair Transplantation. Cambridge University Press. pp. 11–. ISBN 978-1-139-48339-1.
  5. 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. 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. 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. "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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