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{{Short description|Chemical compound}}
{{Distinguish|oxandrolone}}
{{Distinguish|Oxandrolone}}
{{Drugbox
{{Drugbox
| Verifiedfields =
| Verifiedfields =
| Watchedfields =
| Watchedfields =
| verifiedrevid =
| verifiedrevid =
| IUPAC_name = (9''S'',14''S'',17''S'')-16-ethyl-17-hydroxy-13-methyl-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1''H''-cyclopenta[''a'']phenanthren-3-one
⚫
| IUPAC_name = 16β-Ethylestr-4-en-17β-ol-3-one
| image = Oxendolone.svg
| image = Oxendolone.svg
| width =
| width = 225px


<!--Clinical data-->
<!--Clinical data-->
Line 14: Line 15:
| pregnancy_category =
| pregnancy_category =
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| legal_CA =
| legal_CA =
| legal_UK =
| legal_UK =
| legal_US =
| legal_US =
| legal_status =
| legal_status =
| routes_of_administration = [[Intramuscular injection]]<ref name="pmid6131442" /><ref name="pmid26335395" /><ref name="pmid2466359" /><ref name="pmid6419414" />
| routes_of_administration =
| class = [[Steroidal antiandrogen]]; [[Progestogen (medication)|Progestogen]]; [[Progestin]]


<!--Pharmacokinetic data-->
<!--Pharmacokinetic data-->
| bioavailability = [[Oral administration|Oral]]: Very low (1% in dogs)<ref name="RathboneHadgraft2002" />
| bioavailability =
| protein_bound =
| protein_bound =
| metabolism =
| metabolism =
| elimination_half-life = 5–6 days ([[intramuscular injection|intramuscular]])<ref name="GaoBohl2005">{{cite journal|last1=Gao|first1=Wenqing|last2=Bohl|first2=Casey E.|last3=Dalton|first3=James T.|title=Chemistry and Structural Biology of Androgen Receptor|journal=Chemical Reviews|volume=105|issue=9|year=2005|pages=3352–3370|issn=0009-2665|doi=10.1021/cr020456u|pmid=16159155|pmc=2096617}}</ref>
| elimination_half-life = {{abbrlink|IM|Intramuscular injection}}: 5.0–6.6&nbsp;days.<ref name="pmid6419414" /><ref name="GaoBohl2005">{{cite journal | vauthors = Gao W, Bohl CE, Dalton JT | title = Chemistry and structural biology of androgen receptor | journal = Chemical Reviews | volume = 105 | issue = 9 | pages = 3352–3370 | date = September 2005 | pmid = 16159155 | pmc = 2096617 | doi = 10.1021/cr020456u }}</ref>
| excretion =
| excretion =


<!--Identifiers-->
<!--Identifiers-->
| CAS_number_Ref =
| CAS_number_Ref =
| CAS_number = 33765-68-3
| CAS_number = 33765-68-3
| CAS_supplemental =
| CAS_supplemental =
| UNII_Ref = {{fdacite|correct|FDA}}
⚫
| ATC_prefix =
| UNII = MN4I850D4P
⚫
| ATC_suffix =
⚫
| ATC_prefix =
⚫
| ATC_suffix =
| PubChem = 36592
| PubChem = 36592
| DrugBank_Ref =
| DrugBank_Ref =
| DrugBank =
| DrugBank =
| ChemSpiderID_Ref =
| ChemSpiderID_Ref =
| ChemSpiderID = 392001
| ChemSpiderID = 392001
⚫
| synonyms = TSAA-291; 16β-Ethyl-19-nortestosterone; 16β-Ethylestr-4-en-17β-ol-3-one


<!--Chemical data-->
<!--Chemical data-->
| C=20 | H=30 | O=2
| C=20 | H=30 | O=2
⚫
| SMILES = CCC1CC2C3CCC4=CC(=O)CCC4C3CCC2(C1O)C
| molecular_weight = 302.451 g/mol
⚫
| StdInChI_Ref =
⚫
| smiles = CCC1CC2C3CCC4=CC(=O)CCC4C3CCC2(C1O)C
⚫
| StdInChI_Ref =
| StdInChI = 1S/C20H30O2/c1-3-12-11-18-17-6-4-13-10-14(21)5-7-15(13)16(17)8-9-20(18,2)19(12)22/h10,12,15-19,22H,3-9,11H2,1-2H3/t12?,15?,16-,17?,18+,19+,20?/m1/s1
| StdInChI = 1S/C20H30O2/c1-3-12-11-18-17-6-4-13-10-14(21)5-7-15(13)16(17)8-9-20(18,2)19(12)22/h10,12,15-19,22H,3-9,11H2,1-2H3/t12?,15?,16-,17?,18+,19+,20?/m1/s1
| StdInChIKey_Ref =
| StdInChIKey_Ref =
| StdInChIKey = FCKLFGKATYPJPG-LNRSQMQGSA-N
| StdInChIKey = FCKLFGKATYPJPG-LNRSQMQGSA-N
| synonyms =
}}
}}
<!-- Definition and medical uses -->
'''Oxendolone''', sold under the brand names '''Prostetin''' and '''Roxenone''', is an [[antiandrogen]] and [[progestin]] medication which is used in [[Japan]] in the treatment of [[benign prostatic hyperplasia|enlarged prostate]].<ref name="Elks2014">{{cite book| vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA914|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=914–}}</ref><ref name="Publishing2013">{{cite book|author=William Andrew Publishing|title=Pharmaceutical Manufacturing Encyclopedia, 3rd Edition|url=https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA2935-IA129|date=22 October 2013|publisher=Elsevier|isbn=978-0-8155-1856-3|pages=2935–}}</ref><ref name="NegwerScharnow2001">{{cite book| vauthors = Negwer M, Scharnow HG |title=Organic-chemical drugs and their synonyms: (an international survey)|url=https://books.google.com/books?id=zmpqAAAAMAAJ|year=2001|publisher=Wiley-VCH|isbn=978-3-527-30247-5|page=2023}}</ref><ref name="TanLi2014">{{cite journal | vauthors = Tan MH, Li J, Xu HE, Melcher K, Yong EL | title = Androgen receptor: structure, role in prostate cancer and drug discovery | journal = Acta Pharmacologica Sinica | volume = 36 | issue = 1 | pages = 3–23 | date = January 2015 | pmid = 24909511 | pmc = 4571323 | doi = 10.1038/aps.2014.18 }}</ref><ref name="IshizukaNishizawa2002">{{cite journal | vauthors = Ishizuka O, Nishizawa O, Hirao Y, Ohshima S | title = Evidence-based meta-analysis of pharmacotherapy for benign prostatic hypertrophy | journal = International Journal of Urology | volume = 9 | issue = 11 | pages = 607–612 | date = November 2002 | pmid = 12534901 | doi = 10.1046/j.1442-2042.2002.00539.x | doi-access = free }}</ref> However, this use is controversial due to concerns about its clinical efficacy.<ref name="IshizukaNishizawa2002" /> Oxendolone is not effective [[oral administration|by mouth]] and must be given by [[intramuscular injection|injection into muscle]].<ref name="RathboneHadgraft2002" /><ref name="pmid6131442" /><ref name="pmid26335395" /><ref name="pmid2466359" /><ref name="pmid6419414" />


<!-- Side effects and mechanism -->
'''Oxendolone''' ([[International Nonproprietary Name|INN]], [[United States Adopted Name|USAN]], [[Japanese Accepted Name|JAN]]) (brand names '''Prostetin''', '''Roxenone'''; former developmental code name '''TSAA-291'''), also known as '''16β-ethyl-19-nortestosterone''' or '''16β-ethylestr-4-en-17β-ol-3-one''', is a [[steroid]]al [[antiandrogen]] and [[progestin]] of the [[19-nortestosterone]] group that has been marketed in [[Japan]] by [[Takeda]] for the treatment of [[benign prostatic hyperplasia]] (BPH) since 1981.<ref name="Elks2014">{{cite book|author=J. Elks|title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA914|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=914–}}</ref><ref name="Publishing2013">{{cite book|author=William Andrew Publishing|title=Pharmaceutical Manufacturing Encyclopedia, 3rd Edition|url=https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA2935-IA129|date=22 October 2013|publisher=Elsevier|isbn=978-0-8155-1856-3|pages=2935–}}</ref><ref name="NegwerScharnow2001">{{cite book|author1=Martin Negwer|author2=Hans-Georg Scharnow|title=Organic-chemical drugs and their synonyms: (an international survey)|url=https://books.google.com/books?id=zmpqAAAAMAAJ|year=2001|publisher=Wiley-VCH|isbn=978-3-527-30247-5|page=2023}}</ref><ref name="TanLi2014">{{cite journal|last1=Tan|first1=MH Eileen|last2=Li|first2=Jun|last3=Xu|first3=H Eric|last4=Melcher|first4=Karsten|last5=Yong|first5=Eu-leong|title=Androgen receptor: structure, role in prostate cancer and drug discovery|journal=Acta Pharmacologica Sinica|volume=36|issue=1|year=2014|pages=3–23|issn=1671-4083|doi=10.1038/aps.2014.18}}</ref><ref name="IshizukaNishizawa2002">{{cite journal|last1=Ishizuka|first1=Osamu|last2=Nishizawa|first2=Osamu|last3=Hirao|first3=Yoshihiko|last4=Ohshima|first4=Shinichi|title=Evidence-based meta-analysis of pharmacotherapy for benign prostatic hypertrophy|journal=International Journal of Urology|volume=9|issue=11|year=2002|pages=607–612|issn=0919-8172|doi=10.1046/j.1442-2042.2002.00539.x|pmid=12534901}}</ref> It binds to the [[androgen receptor]] (AR) (K<sub>i</sub> = 320 nM) and [[progesterone receptor]] (K<sub>i</sub> = 20 nM) and acts as a weak but clinically relevant [[enzyme inhibitor|inhibitor]] of [[5α-reductase]] ([[IC50|IC<sub>50</sub>]] = 1.4 μM).<ref>{{cite book|title=Annual Reports in Medicinal Chemistry|url=https://books.google.com/books?id=HrALiG-4t7UC&pg=PA199|date=8 September 1989|publisher=Academic Press|isbn=978-0-08-058368-6|pages=199–}}</ref><ref name="Shinogi1991">{{cite book|title=Annual report of Shionogi Research Laboratories|url=https://books.google.com/books?id=kR40AAAAIAAJ|year=1991|pages=76–77}}</ref><ref name="KirbyChristmas1991">{{cite journal|last1=Kirby|first1=RogerS.|last2=Christmas|first2=Timothy|title=The potential value of 5-alpha-reductase inhibition in the treatment of bladder outflow obstruction due to benign prostatic hyperplasia|journal=World Journal of Urology|volume=9|issue=1|year=1991|issn=0724-4983|doi=10.1007/BF00184713}}</ref><ref name="BashirelahiGanesan1986">{{cite journal|last1=Bashirelahi|first1=N.|last2=Ganesan|first2=S.|last3=Ekiko|first3=D.B.|last4=Young|first4=J.D.|last5=Shida|first5=K.|last6=Yamanaka|first6=H.|last7=Takahashi|first7=E.|title=Effect of 16β-ethyl-17β-hydroxy-4-estren-3-one (tsaa-291) on the binding of promegestone (r5020) and methyltrienolone (r1881) to hyperplastic and neoplastic human prostate|journal=Journal of Steroid Biochemistry|volume=25|issue=3|year=1986|pages=367–374|issn=0022-4731|doi=10.1016/0022-4731(86)90249-9}}</ref> The [[binding affinity]] of oxendolone for the AR is far lower than that of [[cyproterone acetate]].<ref name="GaoBohl2005">{{cite journal|last1=Gao|first1=Wenqing|last2=Bohl|first2=Casey E.|last3=Dalton|first3=James T.|title=Chemistry and Structural Biology of Androgen Receptor|journal=Chemical Reviews|volume=105|issue=9|year=2005|pages=3352–3370|issn=0009-2665|doi=10.1021/cr020456u|pmid=16159155|pmc=2096617}}</ref> At the AR, oxendolone is not a [[silent antagonist]] but is rather predominantly antagonistic with weak [[agonist]]ic activity;<ref name="Shinogi1991" /> for this reason, it has been described as a [[selective androgen receptor modulator]].<ref name="HikichiYamaoka2015">{{cite journal|last1=Hikichi|first1=Yukiko|last2=Yamaoka|first2=Masuo|last3=Kusaka|first3=Masami|last4=Hara|first4=Takahito|title=Selective androgen receptor modulator activity of a steroidal antiandrogen TSAA-291 and its cofactor recruitment profile|journal=European Journal of Pharmacology|volume=765|year=2015|pages=322–331|issn=0014-2999|doi=10.1016/j.ejphar.2015.08.052|pmid=26335395}}</ref> The drug has [[antigonadotropic]] properties via its progestogenic actions.<ref name="SudoYamazaki1979">{{cite journal|last1=Sudo|first1=K.|last2=Yamazaki|first2=I.|last3=Masuoka|first3=M.|last4=Nakayama|first4=R.|title=IV. EFFECTS OF THE ANTI-ANDROGEN TSAA-291 (16 -ETHYL-17 -HYDROXY-4-OESTREN-3-ONE) ON THE SECRETION OF GONADOTROPHINS|journal=European Journal of Endocrinology|volume=92|issue=3 Supplb|year=1979|pages=S53–S66|issn=0804-4643|doi=10.1530/acta.0.092S053}}</ref> Although oxendolone is approved for the treatment of BPH in Japan, concerns have been raised about its use for this condition due to poor efficacy seen in [[clinical trial]]s.<ref name="IshizukaNishizawa2002" />
Oxendolone is an [[antiandrogen]], and hence is an [[receptor antagonist|antagonist]] of the [[androgen receptor]], the [[biological target]] of androgens like [[testosterone]] and [[dihydrotestosterone]].<ref name="AcademicPress1989" /><ref name="Shinogi1991" /><ref name="KirbyChristmas1991" /><ref name="BashirelahiGanesan1986" /><ref name="GaoBohl2005" /> It is also a progestin, or a [[synthetic compound|synthetic]] [[progestogen (medication)|progestogen]], and hence is an [[agonist]] of the [[progesterone receptor]], the [[biological target]] of progestogens like [[progesterone]].<ref name="AcademicPress1989" /><ref name="Shinogi1991" /><ref name="KirbyChristmas1991" /><ref name="BashirelahiGanesan1986" /> Due to its progestogenic activity, oxendolone has [[antigonadotropic]] effects.<ref name="SudoYamazaki1979" /><ref name="pmid2435122" /> Oxendolone has no other important [[hormonal agent|hormonal]] activity...


<!-- History, society, and culture -->
==See also==
Oxendolone was introduced for medical use in 1981.<ref name="Publishing2013" /> It is used only in Japan.<ref name="Publishing2013" /><ref name="IshizukaNishizawa2002" />
* [[Benorterone]]
* [[BOMT]]
* [[Cioteronel]]
* [[Osaterone acetate]]
* [[Trimethyltrienolone]]
* [[Zanoterone]]


==References==
==Medical uses==
Oxendolone is used in the treatment of [[benign prostatic hyperplasia]] (BPH) in [[Japan]].<ref name="Publishing2013" /><ref name="IshizukaNishizawa2002" /> It has been used at a dosage of 200&nbsp;mg once every 2&nbsp;weeks via [[intramuscular injection]].<ref name="pmid2435122">{{cite journal | vauthors = Katayama T, Umeda K, Kazama T | title = [Hormonal environment and antiandrogenic treatment in benign prostatic hypertrophy] | language = ja | journal = Hinyokika Kiyo. Acta Urologica Japonica | volume = 32 | issue = 11 | pages = 1584–1589 | date = November 1986 | pmid = 2435122 }}</ref> Although it is approved for the treatment of BPH in Japan, concerns have been raised about its use for this condition due to poor efficacy seen in [[clinical trial]]s.<ref name="IshizukaNishizawa2002" />
⚫
{{Reflist|2}}


==Side effects==
{{See also|Antiandrogen#Side effects|Progestin#Side effects}}

==Pharmacology==

===Pharmacodynamics===
Oxendolone binds to the [[androgen receptor]] (K<sub>i</sub> = 320&nbsp;nM) and [[progesterone receptor]] (K<sub>i</sub> = 20&nbsp;nM) and acts as a weak but clinically relevant [[enzyme inhibitor|inhibitor]] of [[5α-reductase]] ({{abbrlink|IC<sub>50</sub>|half-maximal inhibitory concentration}} = 1.4&nbsp;μM).<ref name="AcademicPress1989">{{cite book | vauthors = Mallamo JP, Juniewicz PE | chapter = New horizons in the treatment of proliferative prostatic disease | veditors = Johns WS |title=Annual Reports in Medicinal Chemistry | chapter-url = https://books.google.com/books?id=HrALiG-4t7UC&pg=PA199 |date=8 September 1989| volume = 24 |publisher=Academic Press|isbn=978-0-08-058368-6|pages=199– | doi = 10.1016/S0065-7743(08)60543-6 }}</ref><ref name="Shinogi1991">{{cite book|title=Annual report of Shionogi Research Laboratories|url=https://books.google.com/books?id=kR40AAAAIAAJ|year=1991|pages=76–77}}</ref><ref name="KirbyChristmas1991">{{cite journal| vauthors = Kirby RS, Christmas T |title=The potential value of 5-alpha-reductase inhibition in the treatment of bladder outflow obstruction due to benign prostatic hyperplasia|journal=World Journal of Urology|volume=9|issue=1|year=1991|issn=0724-4983|doi=10.1007/BF00184713|s2cid=38790542}}</ref><ref name="BashirelahiGanesan1986">{{cite journal | vauthors = Bashirelahi N, Ganesan S, Ekiko DB, Young JD, Shida K, Yamanaka H, Takahashi E | title = Effect of 16 beta-ethyl-17 beta-hydroxy-4-estren-3-one (TSAA-291) on the binding of promegestone (R5020) and methyltrienolone (R1881) to hyperplastic and neoplastic human prostate | journal = Journal of Steroid Biochemistry | volume = 25 | issue = 3 | pages = 367–374 | date = September 1986 | pmid = 2430141 | doi = 10.1016/0022-4731(86)90249-9 }}</ref> The [[relative binding affinity]] of oxendolone for the androgen receptor is 0.8 to 3.6% of that of [[metribolone]].<ref name="DaltonGao2010">{{cite book | vauthors = Dalton J, Gao W | chapter = Androgen Receptor|year=2010|pages=143–182|doi=10.1007/978-90-481-3303-1_6| title = Nuclear Receptors: Current Concepts and Future Challenges | series = Proteins and Cell Regulation| publisher = Springer|isbn=978-90-481-3302-4}}</ref><ref name="pmid7339263">{{cite journal | vauthors = Wakeling AE, Furr BJ, Glen AT, Hughes LR | title = Receptor binding and biological activity of steroidal and nonsteroidal antiandrogens | journal = Journal of Steroid Biochemistry | volume = 15 | pages = 355–359 | date = December 1981 | pmid = 7339263 | doi = 10.1016/0022-4731(81)90297-1 }}</ref> Oxendolone is not a [[silent antagonist]] of the androgen receptor but is rather predominantly antagonistic with weak [[agonist]]ic activity;<ref name="Shinogi1991" /> for this reason, it has been described as a [[selective androgen receptor modulator]].<ref name="HikichiYamaoka2015">{{cite journal | vauthors = Hikichi Y, Yamaoka M, Kusaka M, Hara T | title = Selective androgen receptor modulator activity of a steroidal antiandrogen TSAA-291 and its cofactor recruitment profile | journal = European Journal of Pharmacology | volume = 765 | pages = 322–331 | date = October 2015 | pmid = 26335395 | doi = 10.1016/j.ejphar.2015.08.052 }}</ref> The medication has potent [[antigonadotropic]] effects via its progestogenic activity.<ref name="SudoYamazaki1979">{{cite journal | vauthors = Sudo K, Yamazaki I, Masuoka M, Nakayama R | title = Anti-androgen TSAA-291. IV. Effects of the anti-androgen TSAA-291 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one) on the secretion of gonadotrophins | journal = Acta Endocrinologica. Supplementum | volume = 229 | issue = 3 Supplb | pages = 53–66 | year = 1979 | pmid = 294107 | doi = 10.1530/acta.0.092S053 }}</ref> It has been found to suppress [[luteinizing hormone]] and [[testosterone]] levels to an equivalent extent as [[allylestrenol]] and [[chlormadinone acetate]], which are two progestins that are similarly used at high doses to treat BPH.<ref name="pmid2435122" />

===Pharmacokinetics===
The [[oral administration|oral]] [[bioavailability]] of oxendolone in dogs is extremely low, 1% at most.<ref name="RathboneHadgraft2002">{{cite book| vauthors = Iga K | chapter = Slowly Disintegrating Buccal Mucoadhesive Pain-Tablet (S-DBMP-T) and Buccal Covered=Tablet System (BCTS) | veditors = Rathbone MJ, Hadgraft J, Roberts MS |title=Modified-Release Drug Delivery Technology | chapter-url = https://books.google.com/books?id=mw9W82MLYZ8C&pg=PA368 |date=7 November 2002|publisher=CRC Press|isbn=978-0-8247-0869-6|pages=368–}}</ref> Due to its low oral bioavailability, oxendolone is administered by [[intramuscular injection]] in humans.<ref name="pmid6131442">{{cite journal | vauthors = Henkler G, Klotzbach M, Koch H, Müller W, Richter J | title = [Progress in the area of drug development. 15] | language = de | journal = Die Pharmazie | volume = 37 | issue = 11 | pages = 753–765 | date = November 1982 | pmid = 6131442 | quote = [Oxendolone] has been clinically tested in Japan (weekly intramuscular injection of 200-400 mg) in prostatic hypertrophy. }}</ref><ref name="pmid26335395">{{cite journal | vauthors = Hikichi Y, Yamaoka M, Kusaka M, Hara T | title = Selective androgen receptor modulator activity of a steroidal antiandrogen TSAA-291 and its cofactor recruitment profile | journal = European Journal of Pharmacology | volume = 765 | pages = 322–331 | date = October 2015 | pmid = 26335395 | doi = 10.1016/j.ejphar.2015.08.052 | quote = According to the clinical data of TSAA-291, the plasma level of TSAA-291 after weekly intramuscular administration at 400 mg/kg for 12 weeks is approximately 100 nM (Drug Information). }}</ref><ref name="pmid2466359">{{cite journal | vauthors = Ostri P, Swartz R, Meyhoff HH, Petersen JH, Lindgård G, Frimodt-Møller C, Andersson T, Nielsen MS | display-authors = 6 | title = Antiandrogenic treatment of benign prostatic hyperplasia: a placebo controlled trial | journal = Urological Research | volume = 17 | issue = 1 | pages = 29–33 | year = 1989 | pmid = 2466359 | doi = 10.1007/bf00261046 | quote = Thirty patients were treated with weekly injections of oxendolone 200 mg during a 3 months' period, and 30 patients were allocated to placebo treatment. | s2cid = 30551043 }}</ref><ref name="pmid6419414">{{cite journal | vauthors = Midgley I, Fowkes AG, Darragh A, Lambe R, Chasseaud LF, Taylor T | title = The metabolic fate of the anti-androgenic agent, oxendolone, in man | journal = Steroids | volume = 41 | issue = 4 | pages = 521–536 | date = April 1983 | pmid = 6419414 | doi = 10.1016/0039-128x(83)90092-2 | quote = After intramuscular administration of 16β-ethyl-17β-hydroxy-4-[4-14C] estren-3-one (14C-oxendolone; 300 mg) to 3 human subjects, [...] | s2cid = 41224726 }}</ref> Its [[elimination half-life]] via this route is 5.0 to 6.6&nbsp;days.<ref name="pmid6419414" />

==Chemistry==
{{See also|List of progestogens|Steroidal antiandrogen|List of steroidal antiandrogens}}

Oxendolone, also known as 16β-ethyl-19-nortestosterone or 16β-ethylestr-4-en-17β-ol-3-one, is a [[synthetic compound|synthetic]] [[estrane]] [[steroid]] and a [[chemical derivative|derivative]] of [[testosterone (medication)|testosterone]] and [[19-nortestosterone]] (nandrolone).<ref name="Elks2014" /><ref name="Publishing2013" />

The [[acetate]] [[ester]] of oxendolone is known as TSAA-328, while the [[caproate]] ester of oxendolone is known as TSAA-330.<ref name="pmid294106">{{cite journal | vauthors = Masuoka M, Masaki T, Yamazaki I, Hori T, Nakayama R | title = Anti-androgen TSAA-291. III. Hormonal spectra of anti-androgen TSAA-291 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one) and its derivatives | journal = Acta Endocrinologica. Supplementum | volume = 229 | pages = 36–52 | year = 1979 | pmid = 294106 | doi = 10.1530/acta.0.092s036 }}</ref> They were never marketed.<ref name="pmid294106" />

==History==
Oxendolone has been marketed in [[Japan]] by [[Takeda Pharmaceutical Company|Takeda]] since 1981.<ref name="Publishing2013" />

==Society and culture==

===Generic names===
''Oxendolone'' is the [[generic term|generic name]] of the drug and its {{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|USAN|United States Adopted Name}}, and {{abbrlink|JAN|Japanese Accepted Name}}.<ref name="Elks2014" /><ref name="Drugs.com">{{Cite web|url=https://www.drugs.com/international/oxendolone.html|title=Oxandrolone Uses, Side Effects & Warnings | work = Drugs.com }}</ref> It is also known by its developmental code name ''TSAA-291''.<ref name="Elks2014" /><ref name="Drugs.com" />

===Brand names===
Oxendolone is or has been sold under the brand names Prostetin and Roxenone.<ref name="Elks2014" /><ref name="Drugs.com" />

===Availability===
Oxendolone is marketed only in [[Japan]].<ref name="Drugs.com" />

== References ==
⚫
{{Reflist}}

{{Navboxes
| title = [[Medicine|Medical uses]]
| titlestyle = background:#ccccff
| list1 =
{{Androgens and antiandrogens}}
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{{Progestogens and antiprogestogens}}
{{Drugs used in benign prostatic hypertrophy}}
{{Drugs used in benign prostatic hypertrophy}}
}}
{{Antiandrogens}}
{{Navboxes
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{{Progestogens}}
| title = [[Pharmacodynamics]]
{{Androgenics}}
| titlestyle = background:#ccccff
{{Progestogenics}}
| list1 =
{{Androgen receptor modulators}}
{{Progesterone receptor modulators}}
}}


[[Category:5α-Reductase inhibitors]]
[[Category:5α-Reductase inhibitors]]
[[Category:Antiandrogens]]
[[Category:Secondary alcohols]]
[[Category:Antigonadotropins]]
[[Category:Drugs for benign prostatic hyperplasia]]
[[Category:Drugs for benign prostatic hyperplasia]]
[[Category:Estranes]]
[[Category:Estranes]]
[[Category:Ketones]]
[[Category:Progestogens]]
[[Category:Progestogens]]
[[Category:Steroidal antiandrogens]]


{{steroid-stub}}

Latest revision as of 23:57, 8 December 2023

Not to be confused with Oxandrolone.
Oxendolone
Clinical data
Trade namesProstetin, Roxenone
Other namesTSAA-291; 16β-Ethyl-19-nortestosterone; 16β-Ethylestr-4-en-17β-ol-3-one
Routes of
administration		Intramuscular injection[1][2][3][4]
Drug classSteroidal antiandrogen; Progestogen; Progestin
Pharmacokinetic data
BioavailabilityOral: Very low (1% in dogs)[5]
Elimination half-lifeIMTooltip Intramuscular injection: 5.0–6.6 days.[4][6]
Identifiers
  • (9S,14S,17S)-16-ethyl-17-hydroxy-13-methyl-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-one
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC20H30O2
Molar mass302.458 g·mol−1
3D model (JSmol)
  • CCC1CC2C3CCC4=CC(=O)CCC4C3CCC2(C1O)C
  • InChI=1S/C20H30O2/c1-3-12-11-18-17-6-4-13-10-14(21)5-7-15(13)16(17)8-9-20(18,2)19(12)22/h10,12,15-19,22H,3-9,11H2,1-2H3/t12?,15?,16-,17?,18+,19+,20?/m1/s1
  • Key:FCKLFGKATYPJPG-LNRSQMQGSA-N

Oxendolone, sold under the brand names Prostetin and Roxenone, is an antiandrogen and progestin medication which is used in Japan in the treatment of enlarged prostate.[7][8][9][10][11] However, this use is controversial due to concerns about its clinical efficacy.[11] Oxendolone is not effective by mouth and must be given by injection into muscle.[5][1][2][3][4]

Oxendolone is an antiandrogen, and hence is an antagonist of the androgen receptor, the biological target of androgens like testosterone and dihydrotestosterone.[12][13][14][15][6] It is also a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone.[12][13][14][15] Due to its progestogenic activity, oxendolone has antigonadotropic effects.[16][17] Oxendolone has no other important hormonal activity...

Oxendolone was introduced for medical use in 1981.[8] It is used only in Japan.[8][11]

Medical uses

[edit]

Oxendolone is used in the treatment of benign prostatic hyperplasia (BPH) in Japan.[8][11] It has been used at a dosage of 200 mg once every 2 weeks via intramuscular injection.[17] Although it is approved for the treatment of BPH in Japan, concerns have been raised about its use for this condition due to poor efficacy seen in clinical trials.[11]

Side effects

[edit]
See also: Antiandrogen § Side effects, and Progestin § Side effects

Pharmacology

[edit]

Pharmacodynamics

[edit]

Oxendolone binds to the androgen receptor (Ki = 320 nM) and progesterone receptor (Ki = 20 nM) and acts as a weak but clinically relevant inhibitor of 5α-reductase (IC50Tooltip half-maximal inhibitory concentration = 1.4 μM).[12][13][14][15] The relative binding affinity of oxendolone for the androgen receptor is 0.8 to 3.6% of that of metribolone.[18][19] Oxendolone is not a silent antagonist of the androgen receptor but is rather predominantly antagonistic with weak agonistic activity;[13] for this reason, it has been described as a selective androgen receptor modulator.[20] The medication has potent antigonadotropic effects via its progestogenic activity.[16] It has been found to suppress luteinizing hormone and testosterone levels to an equivalent extent as allylestrenol and chlormadinone acetate, which are two progestins that are similarly used at high doses to treat BPH.[17]

Pharmacokinetics

[edit]

The oral bioavailability of oxendolone in dogs is extremely low, 1% at most.[5] Due to its low oral bioavailability, oxendolone is administered by intramuscular injection in humans.[1][2][3][4] Its elimination half-life via this route is 5.0 to 6.6 days.[4]

Chemistry

[edit]
See also: List of progestogens, Steroidal antiandrogen, and List of steroidal antiandrogens

Oxendolone, also known as 16β-ethyl-19-nortestosterone or 16β-ethylestr-4-en-17β-ol-3-one, is a synthetic estrane steroid and a derivative of testosterone and 19-nortestosterone (nandrolone).[7][8]

The acetate ester of oxendolone is known as TSAA-328, while the caproate ester of oxendolone is known as TSAA-330.[21] They were never marketed.[21]

History

[edit]

Oxendolone has been marketed in Japan by Takeda since 1981.[8]

Society and culture

[edit]

Generic names

[edit]

Oxendolone is the generic name of the drug and its INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name, and JANTooltip Japanese Accepted Name.[7][22] It is also known by its developmental code name TSAA-291.[7][22]

Brand names

[edit]

Oxendolone is or has been sold under the brand names Prostetin and Roxenone.[7][22]

Availability

[edit]

Oxendolone is marketed only in Japan.[22]

References

[edit]
  1. ^ a b c Henkler G, Klotzbach M, Koch H, Müller W, Richter J (November 1982). "[Progress in the area of drug development. 15]". Die Pharmazie (in German). 37 (11): 753–765. PMID 6131442. [Oxendolone] has been clinically tested in Japan (weekly intramuscular injection of 200-400 mg) in prostatic hypertrophy.
  2. ^ a b c Hikichi Y, Yamaoka M, Kusaka M, Hara T (October 2015). "Selective androgen receptor modulator activity of a steroidal antiandrogen TSAA-291 and its cofactor recruitment profile". European Journal of Pharmacology. 765: 322–331. doi:10.1016/j.ejphar.2015.08.052. PMID 26335395. According to the clinical data of TSAA-291, the plasma level of TSAA-291 after weekly intramuscular administration at 400 mg/kg for 12 weeks is approximately 100 nM (Drug Information).
  3. ^ a b c Ostri P, Swartz R, Meyhoff HH, Petersen JH, Lindgård G, Frimodt-Møller C, et al. (1989). "Antiandrogenic treatment of benign prostatic hyperplasia: a placebo controlled trial". Urological Research. 17 (1): 29–33. doi:10.1007/bf00261046. PMID 2466359. S2CID 30551043. Thirty patients were treated with weekly injections of oxendolone 200 mg during a 3 months' period, and 30 patients were allocated to placebo treatment.
  4. ^ a b c d e Midgley I, Fowkes AG, Darragh A, Lambe R, Chasseaud LF, Taylor T (April 1983). "The metabolic fate of the anti-androgenic agent, oxendolone, in man". Steroids. 41 (4): 521–536. doi:10.1016/0039-128x(83)90092-2. PMID 6419414. S2CID 41224726. After intramuscular administration of 16β-ethyl-17β-hydroxy-4-[4-14C] estren-3-one (14C-oxendolone; 300 mg) to 3 human subjects, [...]
  5. ^ a b c Iga K (7 November 2002). "Slowly Disintegrating Buccal Mucoadhesive Pain-Tablet (S-DBMP-T) and Buccal Covered=Tablet System (BCTS)". In Rathbone MJ, Hadgraft J, Roberts MS (eds.). Modified-Release Drug Delivery Technology. CRC Press. pp. 368–. ISBN 978-0-8247-0869-6.
  6. ^ a b Gao W, Bohl CE, Dalton JT (September 2005). "Chemistry and structural biology of androgen receptor". Chemical Reviews. 105 (9): 3352–3370. doi:10.1021/cr020456u. PMC 2096617. PMID 16159155.
  7. ^ a b c d e Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 914–. ISBN 978-1-4757-2085-3.
  8. ^ a b c d e f William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia, 3rd Edition. Elsevier. pp. 2935–. ISBN 978-0-8155-1856-3.
  9. ^ Negwer M, Scharnow HG (2001). Organic-chemical drugs and their synonyms: (an international survey). Wiley-VCH. p. 2023. ISBN 978-3-527-30247-5.
  10. ^ Tan MH, Li J, Xu HE, Melcher K, Yong EL (January 2015). "Androgen receptor: structure, role in prostate cancer and drug discovery". Acta Pharmacologica Sinica. 36 (1): 3–23. doi:10.1038/aps.2014.18. PMC 4571323. PMID 24909511.
  11. ^ a b c d e Ishizuka O, Nishizawa O, Hirao Y, Ohshima S (November 2002). "Evidence-based meta-analysis of pharmacotherapy for benign prostatic hypertrophy". International Journal of Urology. 9 (11): 607–612. doi:10.1046/j.1442-2042.2002.00539.x. PMID 12534901.
  12. ^ a b c Mallamo JP, Juniewicz PE (8 September 1989). "New horizons in the treatment of proliferative prostatic disease". In Johns WS (ed.). Annual Reports in Medicinal Chemistry. Vol. 24. Academic Press. pp. 199–. doi:10.1016/S0065-7743(08)60543-6. ISBN 978-0-08-058368-6.
  13. ^ a b c d Annual report of Shionogi Research Laboratories. 1991. pp. 76–77.
  14. ^ a b c Kirby RS, Christmas T (1991). "The potential value of 5-alpha-reductase inhibition in the treatment of bladder outflow obstruction due to benign prostatic hyperplasia". World Journal of Urology. 9 (1). doi:10.1007/BF00184713. ISSN 0724-4983. S2CID 38790542.
  15. ^ a b c Bashirelahi N, Ganesan S, Ekiko DB, Young JD, Shida K, Yamanaka H, Takahashi E (September 1986). "Effect of 16 beta-ethyl-17 beta-hydroxy-4-estren-3-one (TSAA-291) on the binding of promegestone (R5020) and methyltrienolone (R1881) to hyperplastic and neoplastic human prostate". Journal of Steroid Biochemistry. 25 (3): 367–374. doi:10.1016/0022-4731(86)90249-9. PMID 2430141.
  16. ^ a b Sudo K, Yamazaki I, Masuoka M, Nakayama R (1979). "Anti-androgen TSAA-291. IV. Effects of the anti-androgen TSAA-291 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one) on the secretion of gonadotrophins". Acta Endocrinologica. Supplementum. 229 (3 Supplb): 53–66. doi:10.1530/acta.0.092S053. PMID 294107.
  17. ^ a b c Katayama T, Umeda K, Kazama T (November 1986). "[Hormonal environment and antiandrogenic treatment in benign prostatic hypertrophy]". Hinyokika Kiyo. Acta Urologica Japonica (in Japanese). 32 (11): 1584–1589. PMID 2435122.
  18. ^ Dalton J, Gao W (2010). "Androgen Receptor". Nuclear Receptors: Current Concepts and Future Challenges. Proteins and Cell Regulation. Springer. pp. 143–182. doi:10.1007/978-90-481-3303-1_6. ISBN 978-90-481-3302-4.
  19. ^ Wakeling AE, Furr BJ, Glen AT, Hughes LR (December 1981). "Receptor binding and biological activity of steroidal and nonsteroidal antiandrogens". Journal of Steroid Biochemistry. 15: 355–359. doi:10.1016/0022-4731(81)90297-1. PMID 7339263.
  20. ^ Hikichi Y, Yamaoka M, Kusaka M, Hara T (October 2015). "Selective androgen receptor modulator activity of a steroidal antiandrogen TSAA-291 and its cofactor recruitment profile". European Journal of Pharmacology. 765: 322–331. doi:10.1016/j.ejphar.2015.08.052. PMID 26335395.
  21. ^ a b Masuoka M, Masaki T, Yamazaki I, Hori T, Nakayama R (1979). "Anti-androgen TSAA-291. III. Hormonal spectra of anti-androgen TSAA-291 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one) and its derivatives". Acta Endocrinologica. Supplementum. 229: 36–52. doi:10.1530/acta.0.092s036. PMID 294106.
  22. ^ a b c d "Oxandrolone Uses, Side Effects & Warnings". Drugs.com.
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