Osaterone acetate

Osaterone acetate, sold under the brand name Ypozane, is a medication which is used in veterinary medicine for the treatment of enlarged prostate in dogs.^[3][5][6] It is given by mouth.^[3]

Osaterone acetate

Clinical data
Trade names	Ypozane
Other names	TZP-4238; Gestoxarone acetate; 2-Oxachloromadinone acetate; 17α-Acetoxy-6-chloro-2-oxa-6-dehydroprogesterone; 17α-Acetoxy-6-chloro-2-oxapregna-4,6-diene-3,20-dione, Osaterone acetate (JAN JP)
Routes of administration	By mouth (tablets)
Drug class	Steroidal antiandrogen; Progestogen; Progestin; Progestogen ester
ATCvet code	QG04CX90 (WHO)
Legal status
Legal status	EU: Rx-only[1][2]
Pharmacokinetic data
Protein binding	Osaterone acetate: 90% 15β-Hydroxyosaterone acetate: 80%[3] (Both mainly to albumin)[3]
Metabolism	Liver[3]
Metabolites	15β-Hydroxyosaterone acetate[3]
Elimination half-life	Dogs: 80 hours to 197 ± 109 hours[3][4]
Excretion	Bile: 60%[3] Urine: 25%[3]
Identifiers
IUPAC name [(1R,3aS,3bR,9aR,9bS,11aS)-1-acetyl-5-chloro-9a,11a-dimethyl-7-oxo-2,3,3a,3b,9,9b,10,11-octahydroindeno[4,5-h]isochromen-1-yl] acetate
CAS Number	105149-00-6
PubChem CID	114992
ChemSpider	102924
UNII	FR26FSV5EZ
KEGG	D11105
CompTox Dashboard (EPA)	DTXSID501030455
ECHA InfoCard	100.215.750
Chemical and physical data
Formula	C22H27ClO5
Molar mass	406.90 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC(=O)C1(CCC2C1(CCC3C2C=C(C4=CC(=O)OCC34C)Cl)C)OC(=O)C
InChI InChI=1S/C22H27ClO5/c1-12(24)22(28-13(2)25)8-6-16-14-9-18(23)17-10-19(26)27-11-20(17,3)15(14)5-7-21(16,22)4/h9-10,14-16H,5-8,11H2,1-4H3/t14-,15+,16+,20-,21+,22+/m1/s1 Key:KKTIOMQDFOYCEN-OFUYBIASSA-N

Osaterone acetate is an antiandrogen, and hence is an antagonist of the androgen receptor, the biological target of androgens like testosterone and dihydrotestosterone.^[3] 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.^[3]

Osaterone acetate was introduced for veterinary use in 2007.^[1][3][7][8]

Uses

Veterinary

Osaterone acetate is used in veterinary medicine for the treatment of benign prostatic hyperplasia (BPH) in dogs.^[3][5][6] It has been found to produce remission of clinical symptoms of BPH in 83% of dogs for six months after a single one-week course of treatment,^[9] and can be used long-term.^[6]

Available forms

Osaterone acetate comes in the form of 1.875 mg, 3.75 mg, 7.5 mg, and 15 mg oral tablets for veterinary use.^[3]

Side effects

Side effects of osaterone acetate include diminished sperm quality (for up to 6 weeks post-treatment), transient elevation of liver enzymes (caution should be observed with known liver disease), vomiting, diarrhea, polyuria/polydipsia, lethargy, and hyperplasia of the mammary glands.^[10] It can also decrease cortisol levels, interfere with adrenocorticotropic hormone response, induce or exacerbate adrenal insufficiency, and exacerbate diabetes mellitus.^[11][10]

Pharmacology

Pharmacodynamics

Osaterone acetate is a steroidal antiandrogen, progestin, and antigonadotropin.^[3] It has virtually no estrogenic or androgenic activity.^[5] Its side-effect profile indicates that it possesses clinically relevant glucocorticoid activity.^[11][10] An active metabolite of osaterone acetate, 15β-hydroxyosaterone acetate, has potent antiandrogenic activity similarly to osaterone acetate.^[3] Osaterone acetate treats BPH in dogs by reducing the actions of androgens in the prostate gland.^[3]

Pharmacokinetics

The major active metabolite of osaterone acetate is 15β-hydroxyosaterone acetate.^[3] Osaterone acetate has a long biological half-life of 80 hours to 197 ± 109 hours in dogs.^[3][4]

Chemistry

See also: Steroidal antiandrogen, List of steroidal antiandrogens, List of progestogens, Progestogen ester, and List of progestogen esters

Osaterone acetate, also known as 2-oxachloromadinone acetate, as well as 17α-acetoxy-6-chloro-2-oxa-6-dehydroprogesterone or 17α-acetoxy-6-chloro-2-oxapregna-4,6-diene-3,20-dione, is a synthetic pregnane steroid and a derivative of progesterone and 17α-hydroxyprogesterone.^[8] It is a derivative of the less potent chlormadinone acetate.^[5] The medication is the C17α acetate ester of osaterone.^[8]

History

Osaterone acetate was approved for veterinary use in the European Union under the brand name Ypozane in 2007.^[1][3][7][8]

Society and culture

Generic names

Osaterone acetate is the generic name of the drug.^[1][8] Osaterone is the INNTooltip International Nonproprietary Name of the deacetylated parent compound.^[8]

Brand names

Osaterone acetate is marketed under the brand name Ypozane by Virbac throughout the European Union.^[1][8]

Research

Osaterone acetate was also investigated in Japan in the treatment of prostate cancer and BPH in humans but was ultimately never marketed for such purposes.^[5][12]

References

1. "Ypozane EPAR". European Medicines Agency. 18 January 2007. Retrieved 28 June 2024.
2. "Ypozane PI". Union Register of veterinary medicinal products. 15 January 2007. Retrieved 29 June 2024.
3. "Ypozane for Dogs" (PDF). European Medicines Agency. Archived from the original (PDF) on 20 June 2018. Retrieved 20 February 2018.
4. Maddison JE, Page SW, Church D (2008). Small Animal Clinical Pharmacology. Elsevier Health Sciences. pp. 536–. ISBN 978-0-7020-2858-8.
5. Weber GF (22 July 2015). Molecular Therapies of Cancer. Springer. pp. 316–. ISBN 978-3-319-13278-5.
6. Greer ML (18 December 2014). Canine Reproduction and Neonatology. Teton NewMedia. pp. 296–. ISBN 978-1-4987-2850-8.
7. Emmerich IU, Ungemach FR (2008). "Neue Arzneimittel für Kleintiere 2007". Tierärztliche Praxis Ausgabe K: Kleintiere/Heimtiere. 36 (5): 311–22. doi:10.1055/s-0038-1622691. S2CID 257184365.
8. "Osaterone". Drugs.com.
9. Cote E (9 December 2014). Clinical Veterinary Advisor: Dogs and Cats. Elsevier Health Sciences. pp. 848–. ISBN 978-0-323-24074-1.
10. Lamm C, Makloski C (28 May 2012). Theriogenology, An Issue of Veterinary Clinics: Small Animal Practice. Elsevier Health Sciences. pp. 112–. ISBN 978-1-4557-4447-3.
11. Ettinger SJ, Feldman EC (24 December 2009). Textbook of Veterinary Internal Medicine. Elsevier Health Sciences. pp. 2055–. ISBN 978-1-4377-0282-8.
12. Schröder FH, Radlmaier A (2009). "Steroidal Antiandrogens". In Jordan VC, Furr BJ (eds.). Hormone Therapy in Breast and Prostate Cancer. Cancer Drug Discovery and Development. Humana Press. pp. 325–346. doi:10.1007/978-1-59259-152-7_15. ISBN 978-1-60761-471-5.

Further reading

• Schröder FH, Radlmaier A (2009). "Steroidal Antiandrogens". Hormone Therapy in Breast and Prostate Cancer. Cancer Drug Discovery and Development. Humana Press. pp. 325–346. doi:10.1007/978-1-59259-152-7_15. ISBN 978-1-60761-471-5.