Chemistry:Topilutamide
 | |
| Clinical data | |
|---|---|
| Trade names | Eucapil |
| Other names | Fluridil; BP-766 |
| Routes of administration | Topical[1][2][3][4][5] |
| Drug class | Nonsteroidal antiandrogen |
| ATC code |
|
| Identifiers | |
| |
| CAS Number | |
| PubChem CID | |
| ChemSpider | |
| UNII | |
| Chemical and physical data | |
| Formula | C13H11F6N3O5 |
| Molar mass | 403.237 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
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]
| 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
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 "Fluridil, a rationally designed topical agent for androgenetic alopecia: first clinical experience". Dermatologic Surgery 28 (8): 678–85. August 2002. doi:10.1046/j.1524-4725.2002.02017.x. PMID 12174057.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 Hair Transplantation. Elsevier Health Sciences. 2006. pp. 7–. ISBN 1-4160-3104-9. https://books.google.com/books?id=PXJMqrbk-fAC&pg=PA7.
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 Scripta Medica. 2006. pp. 45, 53–54. https://books.google.com/books?id=ynVRAQAAIAAJ. "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)."
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 Hair Transplantation. Cambridge University Press. 30 November 2009. pp. 11–. ISBN 978-1-139-48339-1. https://books.google.com/books?id=j1XF1bnABFcC&pg=PA11.
- ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 Men's Health, Third Edition. CRC Press. 29 January 2009. pp. 362–. ISBN 978-1-4398-0807-8. https://books.google.com/books?id=e-NyCQAAQBAJ&pg=PA362.
- ↑ 6.00 6.01 6.02 6.03 6.04 6.05 6.06 6.07 6.08 6.09 6.10 6.11 "Development of fluridil, a topical suppressor of the androgen receptor in androgenetic alopecia". Drug Development Research 59 (3): 292–306. 2003. doi:10.1002/ddr.10166. ISSN 0272-4391. https://www.researchgate.net/publication/227651615.
- ↑ 7.0 7.1 7.2 7.3 "Non-steroidal steroid receptor modulators". IDrugs 9 (7): 488–94. July 2006. doi:10.2174/0929867053764671. PMID 16821162.
- ↑ 8.0 8.1 8.2 "Androgenetic Alopecia,Hair loss,Eucapil". http://www.eucapil.com/xhtml_en/eucapil.shtml.
- ↑ "ChemIDplus - 260980-89-0 - YCNCRLKXSLARFT-UHFFFAOYSA-N - Topilutamide [INN - Similar structures search, synonyms, formulas, resource links, and other chemical information."]. https://chem.nlm.nih.gov/chemidplus/rn/260980-89-0.
- ↑ "Microsoft Word - final_PL91.doc". https://www.who.int/medicines/publications/druginformation/innlists/PL91.pdf.
- ↑ 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. https://books.google.com/books?id=nun3ygnC0JoC&pg=PA18.
{{Navbox
| name = Androgens and antiandrogens | title = Androgens and antiandrogens | state = collapsed | listclass = hlist | groupstyle = text-align:center;
| group1 = Androgens
(incl. AAS)
| list1 =
| group2 = Antiandrogens | list2 = {{Navbox|child | groupstyle = text-align:center; | groupwidth = 9em;
| group1 = AR antagonists | list1 =
- Steroidal: Abiraterone acetate
- Canrenone
- Chlormadinone acetate
- Cyproterone acetate
- Delmadinone acetate
- Dienogest
- Drospirenone
- Medrogestone
- Megestrol acetate
- Nomegestrol acetate
- Osaterone acetate
- Oxendolone
- Potassium canrenoate
- Spironolactone
- Nonsteroidal: Apalutamide
- Bicalutamide
- Cimetidine
- Darolutamide
- Enzalutamide
- Flutamide
- Ketoconazole
- Nilutamide
- Seviteronel†
- Topilutamide (fluridil)
| group2 = Steroidogenesis| list2 =
inhibitors
| 5α-Reductase | |
|---|---|
| Others |
| group3 = Antigonadotropins | list3 =
- D2 receptor antagonists (prolactin releasers) (e.g., domperidone, metoclopramide, risperidone, haloperidol, chlorpromazine, sulpiride)
- Estrogens (e.g., bifluranol, [[diethylstilbestrol, estradiol, estradiol esters, ethinylestradiol, ethinylestradiol sulfonate, paroxypropione)
- GnRH agonists (e.g., leuprorelin)
- GnRH antagonists (e.g., cetrorelix)
- Progestogens (incl., chlormadinone acetate, [[cyproterone acetate, hydroxyprogesterone caproate, gestonorone caproate, [[Chemistry:Medroxyprogesterone medroxyprogesterone acetate, Chemistry:Megestrol acetate|megestrol acetate]])
| group4 = Others | list4 =
- Androstenedione immunogens: Androvax (androstenedione albumin)
- Ovandrotone albumin (Fecundin)
}}
| liststyle = background:#DDDDFF;| list3 =
- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
- See also
- Androgen receptor modulators
- Estrogens and antiestrogens
- Progestogens and antiprogestogens
- List of androgens/anabolic steroids
}}
 |  |
