Osaterone acetate

Last updated
Osaterone acetate
Osaterone acetate.svg
Clinical data
Trade names Ypozane
Other namesTZP-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
Routes of
administration 		By mouth (tablets)
Drug class Steroidal antiandrogen; Progestogen; Progestin; Progestogen ester
Pharmacokinetic data
Protein binding Osaterone acetate: 90%
15β-Hydroxyosaterone acetate: 80% [1]
(Both mainly to albumin) [1]
Metabolism Liver [1]
Metabolites 15β-Hydroxyosaterone acetate [1]
Elimination half-life Dogs: 80 hours to 197 ± 109 hours [1] [2]
Excretion Bile: 60% [1]
Urine: 25% [1]
Identifiers
  • [(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
PubChem CID
ChemSpider
UNII
KEGG
ECHA InfoCard 100.215.750 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C22H27ClO5
Molar mass 406.90 g·mol−1
3D model (JSmol)
  • CC(=O)C1(CCC2C1(CCC3C2C=C(C4=CC(=O)OCC34C)Cl)C)OC(=O)C
  • 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, sold under the brand name Ypozane, is a medication which is used in veterinary medicine in Europe in the treatment of enlarged prostate in dogs. [1] [3] [4] It is given by mouth. [1]

Contents

Osaterone acetate is an antiandrogen, and hence is an antagonist of the androgen receptor, the biological target of androgens like testosterone and dihydrotestosterone. [1] 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. [1]

Osaterone acetate was introduced for veterinary use in 2007. [5] It is marketed in Europe. [6] [1]

Uses

Veterinary

Osaterone acetate is used in veterinary medicine in Europe in the treatment of benign prostatic hyperplasia (BPH) in dogs. [1] [3] [4] 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, [7] and can be used long-term. [4]

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. [1]

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. [8] It can also decrease cortisol levels, interfere with adrenocorticotropic hormone response, induce or exacerbate adrenal insufficiency, and exacerbate diabetes mellitus. [9] [8]

Pharmacology

Pharmacodynamics

Osaterone acetate is a steroidal antiandrogen, progestin, and antigonadotropin. [1] It has virtually no estrogenic or androgenic activity. [3] Its side-effect profile indicates that it possesses clinically relevant glucocorticoid activity. [9] [8] An active metabolite of osaterone acetate, 15β-hydroxyosaterone acetate, has potent antiandrogenic activity similarly to osaterone acetate. [1] Osaterone acetate treats BPH in dogs by reducing the actions of androgens in the prostate gland. [1]

Pharmacokinetics

The major active metabolite of osaterone acetate is 15β-hydroxyosaterone acetate. [1] Osaterone acetate has a long biological half-life of 80 hours to 197 ± 109 hours in dogs. [1] [2]

Chemistry

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. [6] It is a derivative of the less potent chlormadinone acetate. [3] The medication is the C17α acetate ester of osaterone. [6]

History

Osaterone acetate was introduced for veterinary use in Europe under the brand name Ypozane in 2007. [6] [5] [1]

Society and culture

Generic names

Osaterone acetate is the generic name of the drug. [6] Osaterone is the INN Tooltip International Nonproprietary Name of the deacetylated parent compound. [6]

Brand names

Osaterone acetate is marketed under the brand name Ypozane by Virbac. [6]

Availability

Osaterone acetate is available widely throughout Europe, including in Belgium, Finland, France, Germany, Italy, the Netherlands, Norway, Poland, Sweden, Switzerland, and the United Kingdom. [6]

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. [3] [10]

Related Research Articles

<span class="mw-page-title-main">Antiandrogen</span> Class of pharmaceutical drugs

Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking the androgen receptor (AR) and/or inhibiting or suppressing androgen production. They can be thought of as the functional opposites of AR agonists, for instance androgens and anabolic steroids (AAS) like testosterone, DHT, and nandrolone and selective androgen receptor modulators (SARMs) like enobosarm. Antiandrogens are one of three types of sex hormone antagonists, the others being antiestrogens and antiprogestogens.

<span class="mw-page-title-main">Nilutamide</span> Chemical compound

Nilutamide, sold under the brand names Nilandron and Anandron, is a nonsteroidal antiandrogen (NSAA) which is used in the treatment of prostate cancer. It has also been studied as a component of feminizing hormone therapy for transgender women and to treat acne and seborrhea in women. It is taken by mouth.

<span class="mw-page-title-main">Megestrol acetate</span> Pharmaceutical drug - appetite stimulant

Megestrol acetate (MGA), sold under the brand name Megace among others, is a progestin medication which is used mainly as an appetite stimulant to treat wasting syndromes such as cachexia. It is also used to treat breast cancer and endometrial cancer, and has been used in birth control. MGA is generally formulated alone, although it has been combined with estrogens in birth control formulations. It is usually taken by mouth.

Feminizing hormone therapy, also known as transfeminine hormone therapy, is hormone therapy and sex reassignment therapy to change the secondary sex characteristics of transgender people from masculine or androgynous to feminine. It is a common type of transgender hormone therapy and is used to treat transgender women and non-binary transfeminine individuals. Some, in particular intersex people but also some non-transgender people, take this form of therapy according to their personal needs and preferences.

<span class="mw-page-title-main">Chlormadinone acetate</span> Chemical compound

Chlormadinone acetate (CMA), sold under the brand names Belara, Gynorelle, Lutéran, and Prostal among others, is a progestin and antiandrogen medication which is used in birth control pills to prevent pregnancy, as a component of menopausal hormone therapy, in the treatment of gynecological disorders, and in the treatment of androgen-dependent conditions like enlarged prostate and prostate cancer in men and acne and hirsutism in women. It is available both at a low dose in combination with an estrogen in birth control pills and, in a few countries like France and Japan, at low, moderate, and high doses alone for various indications. It is taken by mouth.

<span class="mw-page-title-main">Allylestrenol</span> Chemical compound

Allylestrenol, sold under the brand names Gestanin and Turinal among others, is a progestin medication which is used to treat recurrent and threatened miscarriage and to prevent premature labor in pregnant women. However, except in the case of proven progesterone deficiency, its use for such purposes is no longer recommended. It is also used in Japan to treat benign prostatic hyperplasia (BPH) in men. The medication is used alone and is not formulated in combination with an estrogen. It is taken by mouth.

<span class="mw-page-title-main">Cyproterone acetate</span> Chemical compound

Cyproterone acetate (CPA), sold alone under the brand name Androcur or with ethinylestradiol under the brand names Diane or Diane-35 among others, is an antiandrogen and progestin medication used in the treatment of androgen-dependent conditions such as acne, excessive body hair growth, early puberty, and prostate cancer, as a component of feminizing hormone therapy for transgender women, and in birth control pills. It is formulated and used both alone and in combination with an estrogen. CPA is taken by mouth one to three times per day.

<span class="mw-page-title-main">Cyproterone</span> Chemical compound

Cyproterone, also known by its developmental code name SH-80881, is a steroidal antiandrogen which was studied in the 1960s and 1970s but was never introduced for medical use. It is an analogue of cyproterone acetate (CPA), an antiandrogen, progestin, and antigonadotropin which was introduced instead of cyproterone and is widely used as a medication. Cyproterone and CPA were among the first antiandrogens to be developed.

<span class="mw-page-title-main">Delmadinone acetate</span> Chemical compound

Delmadinone acetate (DMA), sold under the brand name Tardak among others, is a progestin and antiandrogen which is used in veterinary medicine to treat androgen-dependent conditions such as benign prostatic hyperplasia. It must be used with care as it has the potential to cause adrenal insufficiency via inhibition of adrenocorticotropic hormone (ACTH) secretion from the pituitary gland. DMA is the C17α acetate ester of delmadinone, which, in contrast to DMA, was never marketed for medical use.

<span class="mw-page-title-main">Benorterone</span> Chemical compound

Benorterone, also known by its developmental code name SKF-7690 and as 17α-methyl-B-nortestosterone, is a steroidal antiandrogen which was studied for potential medical use but was never marketed. It was the first known antiandrogen to be studied in humans. It is taken by mouth or by application to skin.

<span class="mw-page-title-main">Oxendolone</span> Chemical compound

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. However, this use is controversial due to concerns about its clinical efficacy. Oxendolone is not effective by mouth and must be given by injection into muscle.

<span class="mw-page-title-main">Zanoterone</span> Chemical compound

Zanoterone, also known as (5α,17α)-1'-(methylsulfonyl)-1'-H-pregn-20-yno[3,2-c]pyrazol-17-ol, is a steroidal antiandrogen which was never marketed. It was investigated for the treatment of benign prostatic hyperplasia (BPH) but failed to demonstrate sufficient efficacy in phase II clinical trials, and also showed an unacceptable incidence rate and severity of side effects. As such, it was not further developed.

<span class="mw-page-title-main">Nonsteroidal antiandrogen</span> Antiandrogen with a nonsteroidal chemical structure

A nonsteroidal antiandrogen (NSAA) is an antiandrogen with a nonsteroidal chemical structure. They are typically selective and full or silent antagonists of the androgen receptor (AR) and act by directly blocking the effects of androgens like testosterone and dihydrotestosterone (DHT). NSAAs are used in the treatment of androgen-dependent conditions in men and women. They are the converse of steroidal antiandrogens (SAAs), which are antiandrogens that are steroids and are structurally related to testosterone.

<span class="mw-page-title-main">Edogestrone</span> Chemical compound

Edogestrone, or edogesterone, also known as 17α-acetoxy-3,3-ethylenedioxy-6-methylpregn-5-en-20-one, is a steroidal progestin and antiandrogen of the 17α-hydroxyprogesterone group which was synthesized in 1964 but was never marketed. Similarly to the structurally related steroid cyproterone acetate, edogestrone binds directly to the androgen receptor and antagonizes it, displacing androgens like testosterone from the receptor, though not as potently as cyproterone acetate. The drug has also been found to suppress androgen production, likely via progesterone receptor activation-mediated antigonadotropic activity.

<span class="mw-page-title-main">Trimethyltrienolone</span> Chemical compound

Trimethyltrienolone (TMT), also known by its developmental code name R-2956 or RU-2956, is an antiandrogen medication which was never introduced for medical use but has been used in scientific research.

<span class="mw-page-title-main">Steroidal antiandrogen</span> Class of compounds

A steroidal antiandrogen (SAA) is an antiandrogen with a steroidal chemical structure. They are typically antagonists of the androgen receptor (AR) and act both by blocking the effects of androgens like testosterone and dihydrotestosterone (DHT) and by suppressing gonadal androgen production. SAAs lower concentrations of testosterone through simulation of the negative feedback inhibition of the hypothalamus. SAAs are used in the treatment of androgen-dependent conditions in men and women, and are also used in veterinary medicine for the same purpose. They are the converse of nonsteroidal antiandrogens (NSAAs), which are antiandrogens that are not steroids and are structurally unrelated to testosterone.

<span class="mw-page-title-main">Pharmacology of bicalutamide</span>

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<span class="mw-page-title-main">5α-Dihydroethisterone</span> Chemical compound

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<span class="mw-page-title-main">Pharmacology of cyproterone acetate</span>

The pharmacology of cyproterone acetate (CPA) concerns the pharmacology of the steroidal antiandrogen and progestin medication cyproterone acetate.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 "Ypozane for Dogs" (PDF). European Medicines Agency.
  2. 1 2 Maddison JE, Page SW, Church D (2008). Small Animal Clinical Pharmacology. Elsevier Health Sciences. pp. 536–. ISBN   978-0-7020-2858-8.
  3. 1 2 3 4 5 Weber GF (22 July 2015). Molecular Therapies of Cancer. Springer. pp. 316–. ISBN   978-3-319-13278-5.
  4. 1 2 3 Greer ML (18 December 2014). Canine Reproduction and Neonatology. Teton NewMedia. pp. 296–. ISBN   978-1-4987-2850-8.
  5. 1 2 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.
  6. 1 2 3 4 5 6 7 8 "Osaterone". Drugs.com.
  7. ↑ Cote E (9 December 2014). Clinical Veterinary Advisor: Dogs and Cats. Elsevier Health Sciences. pp. 848–. ISBN   978-0-323-24074-1.
  8. 1 2 3 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.
  9. 1 2 Ettinger SJ, Feldman EC (24 December 2009). Textbook of Veterinary Internal Medicine. Elsevier Health Sciences. pp. 2055–. ISBN   978-1-4377-0282-8.
  10. ↑ 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.

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