Topilutamide

Topilutamide
Clinical data
Trade names	Eucapil
Other names	Fluridil; BP-766
Routes of; administration	Topical
Drug class	Nonsteroidal 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	260980-89-0;
PubChem CID	44147451;
ChemSpider	8106619;
UNII	A8EU2FXY13;
ECHA InfoCard	100.245.367
Chemical and physical data
Formula	C13H11F6N3O5
Molar mass	403.237 g·mol−1
3D model (JSmol)	Interactive image;
	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, 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

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 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

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]

References

^ ^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.
^ ^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.
^ ^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).
^ ^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.
^ ^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.
^ ^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.
^ ^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.
^ ^a ^b ^c "Androgenetic Alopecia,Hair loss,Eucapil". www.eucapil.com.
^ 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.
^ "Microsoft Word - final_PL91.doc" (PDF). Retrieved 2018-10-04.
^ 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.