Etynodiol diacetate explained

Width:250
Tradename:Ovulen, Demulen, others
Dailymedid:Ethynodiol
Pregnancy Category:Contraindicated
Routes Of Administration:By mouth
Class:Progestogen
Progestin; Progestogen ester
Atc Prefix:G03
Atc Suffix:DC06
Atc Supplemental:
(with an estrogen)
Legal Au:S4
Legal Us:Rx-only
Legal Us Comment:[1] [2]
Legal Status:Rx-only
Cas Number:297-76-7
Cas Number2:8056-92-6
Pubchem:9270
Drugbank:DB00823
Chemspiderid:8913
Unii:62H10A1236
Kegg:D01294
Chebi:31580
Chembl:1200624
Synonyms:Ethynodiol diacetate; Norethindrol diacetate; 3β-Hydroxynorethisterone 3β,17β-diacetate;[3] 17α-Ethynylestr-4-ene-3β,17β-diyl diacetate; CB-8080; SC-11800
Iupac Name:[(3''S'',8''R'',9''S'',10''R'',13''S'',14''S'',17''R'')-17-acetyloxy-17-ethynyl-13-methyl-2,3,6,7,8,9,10,11,12,14,15,16-dodecahydro-1''H''-cyclopenta[''a'']phenanthren-3-yl] acetate
C:24
H:32
O:4
Smiles:O=C(O[C@@H]4/C=C3\[C@@H]([C@H]2CC[C@]1([C@@H](CC[C@]1(C#C)OC(=O)C)[C@@H]2CC3)C)CC4)C
Stdinchi:1S/C24H32O4/c1-5-24(28-16(3)26)13-11-22-21-8-6-17-14-18(27-15(2)25)7-9-19(17)20(21)10-12-23(22,24)4/h1,14,18-22H,6-13H2,2-4H3/t18-,19-,20+,21+,22-,23-,24-/m0/s1
Stdinchikey:ONKUMRGIYFNPJW-KIEAKMPYSA-N

Etynodiol diacetate, or ethynodiol diacetate, sold under the brand name Ovulen among others, is a progestin medication which is used in birth control pills.[4] [5] [6] The medication is available only in combination with an estrogen.[7] It is taken by mouth.

Etynodiol diacetate is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone. It has weak androgenic and estrogenic activity and no other important hormonal activity. The medication is a prodrug of norethisterone in the body, with etynodiol occurring as an intermediate.

Etynodiol, a related compound, was discovered in 1954, and etynodiol diacetate was introduced for medical use in 1965. The combination ethynodiol with mestranol (Ovulen) was approved for medical use in the United States in 1966.[8] The combination ethinylestradiol with ethynodiol (Demulen) was approved for medical use in the United States in 1970.[9]

In 2021, the combination with ethinylestradiol was the 276th most commonly prescribed medication in the United States, with more than 800,000 prescriptions.[10] [11]

Medical uses

Etynodiol diacetate is used in combination with an estrogen such as ethinylestradiol or mestranol in combined oral contraceptives for women for the prevention of pregnancy.[12]

Pharmacology

Etynodiol diacetate is virtually inactive in terms of affinity for the progesterone and androgen receptors and acts as a rapidly converted prodrug of norethisterone, with etynodiol occurring as an intermediate.[13] [14] [15] Upon oral administration and during first-pass metabolism in the liver, etynodiol diacetate is rapidly converted by esterases into etynodiol, which is followed by oxygenation of the C3 hydroxyl group to produce norethisterone. In addition to its progestogenic activity, etynodiol diacetate has weak androgenic activity,[16] [17] and, unlike most progestins but similarly to norethisterone and noretynodrel,[18] also has some estrogenic activity.[19]

The pharmacokinetics of etynodiol diacetate have been reviewed.

Chemistry

See also: List of progestogens, Progestogen ester and List of progestogen esters.

Etynodiol diacetate, also known as 3β-hydroxy-17α-ethynyl-19-nortestosterone 3β,17β-diaceate, 3β-hydroxynorethisterone 3β,17β-diacetate, or 17α-ethynylestr-4-ene-3β,17β-diol 3β,17β-diacetate, is a synthetic estrane steroid and a derivative of testosterone. It is specifically a derivative of 19-nortestosterone and 17α-ethynyltestosterone, or of norethisterone (17α-ethynyl-19-nortestosterone), in which the C3 ketone group has been dehydrogenated into a C3β hydroxyl group and acetate esters have been attached at the C3β and C17β positions. Etynodiol diacetate is the 3β,17β-diacetate ester of etynodiol (17α-ethynylestr-4-ene-3β,17β-diol).

Synthesis

Chemical syntheses of etynodiol diacetate have been published.[20]

Reduction of norethisterone (1) affords the 3,17-diol. The 3β-hydroxy compound is the desired product; since reactions at C3 do not show nearly the stereoselectivity as those at C17 by virtue of the relative lack of stereo-directing proximate substituents, the formation of the desired isomer is engendered by use of a bulky reducing agent, lithium tri-tert-butoxyaluminum hydride. Acetylation of the 3β,17β-diol affords etynodiol diacetate (3).

History

Etynodiol was first synthesized in 1954, via reduction of norethisterone, and etynodiol diacetate was introduced for medical use in 1965.[21] [22]

Society and culture

Generic names

Etynodiol diacetate is the generic name of the drug (the of its free alcohol form is etynodiol), while ethynodiol diacetate is its,, and . It is also known by its former developmental code names CB-8080 and SC-11800.

Brand names

Etynodiol diacetate is or has been marketed under brand names including Conova, Continuin, Demulen,[23] Femulen, Kelnor, Lo-Malmorede,[24] Luteonorm, Luto-Metrodiol, Malmorede,[25] Metrodiol, Ovulen, Soluna, Zovia, and others.

Availability

Etynodiol diacetate is marketed in only a few countries, including the United States, Canada, Argentina, and Oman.

Notes and References

  1. Web site: Zovia 1/35- ethynodiol diacetate and ethinyl estradiol tablets kit . 20 January 2024 . 28 September 2022 . https://web.archive.org/web/20220928055344/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d0d2a9e9-e9ce-4a42-b429-5c1f9a544795 . live .
  2. Web site: Kelnor 1/35- ethynodiol diacetate and ethinyl estradiol kit . 20 January 2024 . 29 March 2023 . https://web.archive.org/web/20230329223042/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=96a73786-22b1-457e-be73-80b699996d40 . live .
  3. Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH . Classification and pharmacology of progestins . Maturitas . 46 . Suppl 1 . S7–S16 . December 2003 . 14670641 . 10.1016/j.maturitas.2003.09.014 .
  4. Book: Shoupe D, Haseltine FP . Contraception. 6 December 2012. Springer Science & Business Media. 978-1-4612-2730-4. 21–.
  5. Book: Elks J . The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. 14 November 2014. Springer. 978-1-4757-2085-3. 522–.
  6. Book: Index Nominum 2000: International Drug Directory . 30 May 2012 . 2000 . Taylor & Francis US . 978-3-88763-075-1 . 422.
  7. Web site: Etynodiol . Drugs.com . 4 February 2018 . 5 February 2018 . https://web.archive.org/web/20180205072835/https://www.drugs.com/international/etynodiol.html . dead .
  8. Web site: Ovulen: FDA-Approved Drugs . U.S. Food and Drug Administration (FDA) . 20 January 2024 . 8 December 2022 . https://web.archive.org/web/20221208200534/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=016029 . live .
  9. Web site: Demulen: FDA-Approved Drugs . U.S. Food and Drug Administration (FDA) . 20 January 2024 . 10 May 2021 . https://web.archive.org/web/20210510195329/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=016927 . live .
  10. Web site: The Top 300 of 2021 . ClinCalc . 14 January 2024 . 15 January 2024 . https://web.archive.org/web/20240115223848/https://clincalc.com/DrugStats/Top300Drugs.aspx . live .
  11. Web site: Ethinyl Estradiol; Ethynodiol - Drug Usage Statistics . ClinCalc . 14 January 2024 . 18 January 2024 . https://web.archive.org/web/20240118044937/https://clincalc.com/DrugStats/Drugs/EthinylEstradiolEthynodiol . live .
  12. Book: Blum RW . Adolescent Health Care: Clinical Issues. 22 October 2013. Elsevier Science. 978-1-4832-7738-7. 216–.
  13. Hammerstein J . Prodrugs: advantage or disadvantage? . American Journal of Obstetrics and Gynecology . 163 . 6 Pt 2 . 2198–2203 . December 1990 . 2256526 . 10.1016/0002-9378(90)90561-K .
  14. Book: IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. World Health Organization. International Agency for Research on Cancer. Combined Estrogen-progestogen Contraceptives and Combined Estrogen-progestogen Menopausal Therapy. 2007. World Health Organization. 978-92-832-1291-1. 146–.
  15. Stanczyk FZ . Pharmacokinetics and potency of progestins used for hormone replacement therapy and contraception . Reviews in Endocrine & Metabolic Disorders . 3 . 3 . 211–224 . September 2002 . 12215716 . 10.1023/A:1020072325818 . 27018468 .
  16. Book: Tashjian AH, Armstrong EJ. Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy. 21 July 2011. Lippincott Williams & Wilkins. 978-1-4511-1805-6. 523–. 11 October 2016. 11 January 2023. https://web.archive.org/web/20230111061913/https://books.google.com/books?id=kjCCMZHInigC&pg=PA523. live.
  17. Book: Becker KL . Principles and Practice of Endocrinology and Metabolism . 30 May 2012 . 24 April 2001 . Lippincott Williams & Wilkins . 978-0-7817-1750-2 . 1004.
  18. Book: Runnebaum BC, Rabe T, Kiesel L . Female Contraception: Update and Trends. 6 December 2012. Springer Science & Business Media. 978-3-642-73790-9. 36–.
  19. Book: Goroll AH, Mulley AG . Primary Care Medicine: Office Evaluation and Management of the Adult Patient . 30 May 2012 . 27 January 2009 . Lippincott Williams & Wilkins . 978-0-7817-7513-7 . 876.
  20. Book: Konstitution J . Handbuch der Experimentellen Pharmakologie . Eigenschaften der Gestagene . https://books.google.com/books?id=t8GpBgAAQBAJ&pg=PA14. 27 November 2013. Springer-Verlag. 978-3-642-99941-3. 14–15,286 . Cham .
  21. Petrow V . Antifertility agents . Progress in Medicinal Chemistry . 8 . 2 . 171–229 . 1971 . 4947236 . 10.1016/s0079-6468(08)70130-9 . 9780408703147 .
  22. Book: William Andrew Publishing. Pharmaceutical Manufacturing Encyclopedia, 3rd Edition. 22 October 2013. Elsevier. 978-0-8155-1856-3. 1516–. 4 February 2018. 20 January 2024. https://web.archive.org/web/20240120214214/https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA1516#v=onepage&q&f=false. live.
  23. Web site: Estrogen and Progestin (Oral Contraceptives) . 20 January 2024 . 18 January 2024 . https://web.archive.org/web/20240118202230/https://medlineplus.gov/druginfo/meds/a601050.html . live .
  24. Web site: Lo-Malmorede . 20 January 2024 . 24 March 2021 . https://web.archive.org/web/20210324212006/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=209548 . live .
  25. Web site: Malmorede . 20 January 2024 . 1 October 2023 . https://web.archive.org/web/20231001024659/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=209547 . live .

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