Chemistry:Levonorgestrel butanoate

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Short description: Chemical compound
Levonorgestrel butanoate
Levonorgestrel butanoate.svg
Clinical data
Other namesLNG-B; HRP-002; Levonorgestrel 17β-butanoate; 17α-Ethynyl-18-methyl-19-nortestosterone 17β-butanoate; 17α-Ethynyl-18-methylestr-4-en-17β-ol-3-one 17β-butanoate
Routes of
administration		Intramuscular injection
Drug classProgestogen; Progestogen ester
ATC code
  • None
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC25H34O3
Molar mass382.544 g·mol−1
3D model (JSmol)

Levonorgestrel butanoate (LNG-B) (developmental code name HRP-002),[1][2] or levonorgestrel 17β-butanoate, is a steroidal progestin of the 19-nortestosterone group which was developed by the World Health Organization (WHO) in collaboration with the Contraceptive Development Branch (CDB) of the National Institute of Child Health and Human Development as a long-acting injectable contraceptive.[3][4][5] It is the C17β butanoate ester of levonorgestrel, and acts as a prodrug of levonorgestrel in the body.[4] The drug is at or beyond the phase III stage of clinical development, but has not been marketed at this time.[3] It was first described in the literature, by the WHO, in 1983, and has been under investigation for potential clinical use since then.[4][6]

LNG-B has been under investigation as a long-lasting injectable contraceptive for women.[7] A single intramuscular injection of an aqueous suspension of 5 or 10 mg LNG-B has a duration of 3 months,[3][7] whereas an injection of 50 mg has a duration of 6 months.[1] The drug was also previously tested successfully as a combined injectable contraceptive with estradiol hexahydrobenzoate, but this formulation was never marketed.[7] LNG-B has been tested successfully in combination with testosterone buciclate as a long-lasting injectable contraceptive for men as well.[8][9]

LNG-B may have several advantages over depot medroxyprogesterone acetate, including the use of much lower comparative dosages, reduced progestogenic side effects like hypogonadism and amenorrhea, and a more rapid return in fertility following discontinuation.[7][10] The drug has a well-established safety record owing to the use of levonorgestrel as an oral contraceptive since the 1960s.[7]

Parenteral potencies and durations of progestogens[lower-alpha 1][lower-alpha 2]
Compound Form Dose for specific uses (mg)[lower-alpha 3] DOA[lower-alpha 4]
TFD[lower-alpha 5] POICD[lower-alpha 6] CICD[lower-alpha 7]
Algestone acetophenide Oil soln. - – 75–150 14–32 d
Gestonorone caproate Oil soln. 25–50 – – 8–13 d
Hydroxyprogest. acetate[lower-alpha 8] Aq. susp. 350 – – 9–16 d
Hydroxyprogest. caproate Oil soln. 250–500[lower-alpha 9] – 250–500 5–21 d
Medroxyprog. acetate Aq. susp. 50–100 150 25 14–50+ d
Megestrol acetate Aq. susp. - – 25 >14 d
Norethisterone enanthate Oil soln. 100–200 200 50 11–52 d
Progesterone Oil soln. 200[lower-alpha 9] – – 2–6 d
Aq. soln. ? – – 1–2 d
Aq. susp. 50–200 – – 7–14 d
Notes and sources:
  1. ↑ Sources: [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][3][7][1]
  2. ↑ All given by intramuscular or subcutaneous injection.
  3. ↑ Progesterone production during the luteal phase is ~25 (15–50) mg/day. The OID of OHPC is 250 to 500 mg/month.
  4. ↑ Duration of action in days.
  5. ↑ Usually given for 14 days.
  6. ↑ Usually dosed every two to three months.
  7. ↑ Usually dosed once monthly.
  8. ↑ Never marketed or approved by this route.
  9. ↑ 9.0 9.1 In divided doses (2 × 125 or 250 mg for OHPC, 10 × 20 mg for P4).

See also

References

  1. ↑ 1.0 1.1 1.2 Varney's Midwifery. Jones & Bartlett Publishers. 21 October 2013. pp. 495–. ISBN 978-1-284-02542-2. https://books.google.com/books?id=dbaNAQAAQBAJ&pg=PA495. 
  2. ↑ Pharmacology, Biology, and Clinical Applications of Androgens: Current Status and Future Prospects. John Wiley & Sons. 13 February 1996. pp. 401–. ISBN 978-0-471-13320-9. https://books.google.com/books?id=hurRyWje4DMC&pg=PA401. 
  3. ↑ 3.0 3.1 3.2 3.3 Female Contraception: Update and Trends. Springer Science & Business Media. 6 December 2012. pp. 429–. ISBN 978-3-642-73790-9. https://books.google.com/books?id=LtT6CAAAQBAJ&pg=PA429. 
  4. ↑ 4.0 4.1 4.2 "Long-acting contraceptive agents: design of the WHO Chemical Synthesis Programme". Steroids 41 (3): 243–53. 1983. doi:10.1016/0039-128X(83)90095-8. PMID 6658872. 
  5. ↑ "The injectable contraceptive: present and future trends". Ann. N. Y. Acad. Sci. 626 (1): 30–42. 1991. doi:10.1111/j.1749-6632.1991.tb37897.x. PMID 1829341. Bibcode: 1991NYASA.626...30K. 
  6. ↑ Benagiano, G., & Merialdi, M. (2011). Carl Djerassi and the World Health Organisation special programme of research in human reproduction. Journal für Reproduktionsmedizin und Endokrinologie-Journal of Reproductive Medicine and Endocrinology, 8(1), 10-13. http://www.kup.at/kup/pdf/10163.pdf
  7. ↑ 7.0 7.1 7.2 7.3 7.4 7.5 Advances in Gynecological Endocrinology. CRC Press. 11 December 2001. pp. 105–. ISBN 978-1-84214-071-0. https://books.google.com/books?id=dknDdAonzlUC&pg=PA105. 
  8. ↑ New Horizons in Reproductive Medicine. CRC Press. 15 August 1997. pp. 101–. ISBN 978-1-85070-793-6. https://books.google.com/books?id=dmokq_M-gm8C&pg=PA101. 
  9. ↑ Mammalian Endocrinology and Male Reproductive Biology. CRC Press. 4 September 2015. pp. 270–. ISBN 978-1-4987-2736-5. https://books.google.com/books?id=Y-KYCgAAQBAJ&pg=PA270. 
  10. ↑ Atlas of Contraception, Second Edition. CRC Press. 14 April 2008. pp. 49–. ISBN 978-0-203-34732-4. https://books.google.com/books?id=7dDKBQAAQBAJ&pg=PA49. 
  11. ↑ Lehrbuch der Gynäkologie. Springer-Verlag. 17 April 2013. pp. 214–. ISBN 978-3-662-00942-0. https://books.google.com/books?id=ACybBwAAQBAJ&pg=PA214. 
  12. ↑ Geburtshilfe und Gynäkologie: Physiologie und Pathologie der Reproduktion. Springer-Verlag. 8 March 2013. pp. 583–. ISBN 978-3-642-95583-9. https://books.google.com/books?id=tpmgBgAAQBAJ&pg=PA583. 
  13. ↑ Clinical Endocrinology: Theory and Practice. Springer Science & Business Media. 6 December 2012. pp. 554–. ISBN 978-3-642-96158-8. https://books.google.com/books?id=DAgJCAAAQBAJ&pg=PA554. 
  14. ↑ "Hormonal Treatment of Disorders of the Menstrual Cycle". Ovarian Function and its Disorders: Diagnosis and Therapy. Developments in Obstetrics and Gynecology. Springer Science & Business Media. 1981. pp. 309–332. doi:10.1007/978-94-009-8195-9_11. ISBN 978-94-009-8195-9. https://books.google.com/books?id=7IrpCAAAQBAJ&pg=PA313. 
  15. ↑ The Principles and Practice of Hormone Therapy in Gynaecology and Obstetrics. de Gruyter. 1969. p. 49. ISBN 9783110006148. https://books.google.com/books?id=G8VsAAAAMAAJ. "17α-Hydroxyprogesterone caproate is a depot progestogen which is entirely free of side actions. The dose required to induce secretory changes in primed endometrium is about 250 mg. per menstrual cycle." 
  16. ↑ Praktische Gynäkologie: für Studierende und Ärzte. Walter de Gruyter. 1968. pp. 598,601. ISBN 978-3-11-150424-7. https://books.google.com/books?id=vVaTnHDFzZ0C&pg=PA598. 
  17. ↑ "Effects, Duration of Action and Metabolism in Man". Pharmacology of the Endocrine System and Related Drugs: Progesterone, Progestational Drugs and Antifertility Agents. II. Pergamon Press. September 1972. pp. 13–24. ISBN 978-0080168128. OCLC 278011135. https://books.google.com/books?id=Nv5sAAAAMAAJ. 
  18. ↑ "Pharmacology of Progestins: 17α-Hydroxyprogesterone Derivatives and Progestins of the First and Second Generation". Progestins and Antiprogestins in Clinical Practice. Taylor & Francis. 10 November 1999. pp. 101–132. ISBN 978-0-8247-8291-7. https://books.google.com/books?id=vGJJHsJASekC. 
  19. ↑ Sex Hormone Pharmacology. Academic Press. 1976. p. 114. ISBN 978-0-12-137250-7. https://books.google.com/books?id=zt5sAAAAMAAJ. 
  20. ↑ "Pharmacodynamic effects of once-a-month combined injectable contraceptives". Contraception 49 (4): 361–85. April 1994. doi:10.1016/0010-7824(94)90033-7. PMID 8013220. 
  21. ↑ "Existing once-a-month combined injectable contraceptives". Contraception 49 (4): 293–301. April 1994. doi:10.1016/0010-7824(94)90029-9. PMID 8013216. 
  22. ↑ "Increasing use of long-acting reversible contraception: safe, reliable, and cost-effective birth control". World J Pharm Pharm Sci 3 (10): 364–392. 2014. ISSN 2278-4357. http://www.wjpps.com/download/article/1412071798.pdf. Retrieved 2016-08-24. 
  23. ↑ "Pharmacokinetics of Contraceptive Steroids in Humans". Contraceptive Steroids: Pharmacology and Safety. Reproductive Biology. Springer Science & Business Media. 1986. pp. 67–111. doi:10.1007/978-1-4613-2241-2_4. ISBN 978-1-4613-2241-2. https://books.google.com/books?id=7dnTBwAAQBAJ&pg=PA67. 
  24. ↑ "[Bioavailability of cyproterone acetate after oral and intramuscular application in men (author's transl)]". Urologia Internationalis 35 (6): 381–5. 1980. doi:10.1159/000280353. PMID 6452729. 
  25. ↑ "[Treatment of virilized women with intramuscular administration of cyproterone acetate]". Geburtshilfe und Frauenheilkunde 43 (5): 281–7. May 1983. doi:10.1055/s-2008-1036893. PMID 6223851. 
  26. ↑ Long Acting Injections and Implants. Springer Science & Business Media. 29 January 2012. pp. 114–. ISBN 978-1-4614-0554-2. https://books.google.com/books?id=36nkGjEGEToC&pg=PA114. 
  27. ↑ "Pharmacokinetics of megestrol acetate in women receiving IM injection of estradiol-megestrol long-acting injectable contraceptive". The Chinese Journal of Clinical Pharmacology. April 1986. http://en.cnki.com.cn/Article_en/CJFDTOTAL-GLYZ198604003.htm. "The results showed that after injection the concentration of plasma MA increased rapidly. The meantime of peak plasma MA level was 3rd day, there was a linear relationship between log of plasma MA concentration and time (day) after administration in all subjects, elimination phase half-life t1/2β = 14.35 ± 9.1 days.". 




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