Levonorgestrel butanoate
Clinical data | |
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Other names | LNG-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 class | Progestogen; Progestogen ester |
ATC code |
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Identifiers | |
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CAS Number | |
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CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.081.125 |
Chemical and physical data | |
Formula | C25H34O3 |
Molar mass | 382.544 g·mol−1 |
3D model (JSmol) | |
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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]
Compound | Form | Dose for specific uses (mg)[c] | DOA[d] | |||
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TFD[e] | POICD[f] | CICD[g] | ||||
Algestone acetophenide | Oil soln. | - | – | 75–150 | 14–32 d | |
Gestonorone caproate | Oil soln. | 25–50 | – | – | 8–13 d | |
Hydroxyprogest. acetate[h] | Aq. susp. | 350 | – | – | 9–16 d | |
Hydroxyprogest. caproate | Oil soln. | 250–500[i] | – | 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[i] | – | – | 2–6 d | |
Aq. soln. | ? | – | – | 1–2 d | ||
Aq. susp. | 50–200 | – | – | 7–14 d | ||
Notes and sources:
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See also
[edit]- List of progestogen esters § Esters of 19-nortestosterone derivatives
- Progestogen-only injectable contraceptive
- Special Programme on Human Reproduction
References
[edit]- ^ a b c King TL, Brucker MC, Kriebs JM, Fahey JO (21 October 2013). Varney's Midwifery. Jones & Bartlett Publishers. pp. 495–. ISBN 978-1-284-02542-2.
- ^ Bhasin S (13 February 1996). Pharmacology, Biology, and Clinical Applications of Androgens: Current Status and Future Prospects. John Wiley & Sons. pp. 401–. ISBN 978-0-471-13320-9.
- ^ a b c d Runnebaum BC, Rabe T, Kiesel L (6 December 2012). Female Contraception: Update and Trends. Springer Science & Business Media. pp. 429–. ISBN 978-3-642-73790-9.
- ^ a b c Crabbé P, Archer S, Benagiano G, Diczfalusy E, Djerassi C, Fried J, Higuchi T (1983). "Long-acting contraceptive agents: design of the WHO Chemical Synthesis Programme". Steroids. 41 (3): 243–53. doi:10.1016/0039-128X(83)90095-8. PMID 6658872. S2CID 12896179.
- ^ Koetsawang S (1991). "The injectable contraceptive: present and future trends". Ann. N. Y. Acad. Sci. 626 (1): 30–42. Bibcode:1991NYASA.626...30K. doi:10.1111/j.1749-6632.1991.tb37897.x. PMID 1829341. S2CID 27008012.
- ^ 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
- ^ a b c d e f Artini PG, Genazzani AR, Petraglia F (11 December 2001). Advances in Gynecological Endocrinology. CRC Press. pp. 105–. ISBN 978-1-84214-071-0.
- ^ Coutifaris C, Mastroianni L (15 August 1997). New Horizons in Reproductive Medicine. CRC Press. pp. 101–. ISBN 978-1-85070-793-6.
- ^ Singh SK (4 September 2015). Mammalian Endocrinology and Male Reproductive Biology. CRC Press. pp. 270–. ISBN 978-1-4987-2736-5.
- ^ Senanayake P, Potts M (14 April 2008). Atlas of Contraception, Second Edition. CRC Press. pp. 49–. ISBN 978-0-203-34732-4.
- ^ Knörr K, Beller FK, Lauritzen C (17 April 2013). Lehrbuch der Gynäkologie. Springer-Verlag. pp. 214–. ISBN 978-3-662-00942-0.
- ^ Knörr K, Knörr-Gärtner H, Beller FK, Lauritzen C (8 March 2013). Geburtshilfe und Gynäkologie: Physiologie und Pathologie der Reproduktion. Springer-Verlag. pp. 583–. ISBN 978-3-642-95583-9.
- ^ Labhart A (6 December 2012). Clinical Endocrinology: Theory and Practice. Springer Science & Business Media. pp. 554–. ISBN 978-3-642-96158-8.
- ^ Horský J, Presl J (1981). "Hormonal Treatment of Disorders of the Menstrual Cycle". In Horsky J, Presl K (eds.). Ovarian Function and its Disorders: Diagnosis and Therapy. Developments in Obstetrics and Gynecology. Springer Science & Business Media. pp. 309–332. doi:10.1007/978-94-009-8195-9_11. ISBN 978-94-009-8195-9.
- ^ Ufer J (1969). The Principles and Practice of Hormone Therapy in Gynaecology and Obstetrics. de Gruyter. p. 49. ISBN 9783110006148.
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.
- ^ Pschyrembel W (1968). Praktische Gynäkologie: für Studierende und Ärzte. Walter de Gruyter. pp. 598, 601. ISBN 978-3-11-150424-7.
- ^ Ferin J (September 1972). "Effects, Duration of Action and Metabolism in Man". In Tausk M (ed.). Pharmacology of the Endocrine System and Related Drugs: Progesterone, Progestational Drugs and Antifertility Agents. Vol. II. Pergamon Press. pp. 13–24. ISBN 978-0080168128. OCLC 278011135.
- ^ Henzl MR, Edwards JA (10 November 1999). "Pharmacology of Progestins: 17α-Hydroxyprogesterone Derivatives and Progestins of the First and Second Generation". In Sitruk-Ware R, Mishell DR (eds.). Progestins and Antiprogestins in Clinical Practice. Taylor & Francis. pp. 101–132. ISBN 978-0-8247-8291-7.
- ^ Brotherton J (1976). Sex Hormone Pharmacology. Academic Press. p. 114. ISBN 978-0-12-137250-7.
- ^ Sang GW (April 1994). "Pharmacodynamic effects of once-a-month combined injectable contraceptives". Contraception. 49 (4): 361–85. doi:10.1016/0010-7824(94)90033-7. PMID 8013220.
- ^ Toppozada MK (April 1994). "Existing once-a-month combined injectable contraceptives". Contraception. 49 (4): 293–301. doi:10.1016/0010-7824(94)90029-9. PMID 8013216.
- ^ Bagade O, Pawar V, Patel R, Patel B, Awasarkar V, Diwate S (2014). "Increasing use of long-acting reversible contraception: safe, reliable, and cost-effective birth control" (PDF). World J Pharm Pharm Sci. 3 (10): 364–392. ISSN 2278-4357. Archived from the original (PDF) on 2017-08-10. Retrieved 2016-08-24.
- ^ Goebelsmann U (1986). "Pharmacokinetics of Contraceptive Steroids in Humans". In Gregoire AT, Blye RP (eds.). Contraceptive Steroids: Pharmacology and Safety. Reproductive Biology. Springer Science & Business Media. pp. 67–111. doi:10.1007/978-1-4613-2241-2_4. ISBN 978-1-4613-2241-2.
- ^ Becker H, Düsterberg B, Klosterhalfen H (1980). "[Bioavailability of cyproterone acetate after oral and intramuscular application in men (author's transl)]" [Bioavailability of Cyproterone Acetate after Oral and Intramuscular Application in Men]. Urologia Internationalis. 35 (6): 381–5. doi:10.1159/000280353. PMID 6452729.
- ^ Moltz L, Haase F, Schwartz U, Hammerstein J (May 1983). "[Treatment of virilized women with intramuscular administration of cyproterone acetate]" [Efficacy of Intra muscularly Applied Cyproterone Acetate in Hyperandrogenism]. Geburtshilfe und Frauenheilkunde. 43 (5): 281–7. doi:10.1055/s-2008-1036893. PMID 6223851. S2CID 260160042.
- ^ Wright JC, Burgess DJ (29 January 2012). Long Acting Injections and Implants. Springer Science & Business Media. pp. 114–. ISBN 978-1-4614-0554-2.
- ^ Chu YH, Li Q, Zhao ZF (April 1986). "Pharmacokinetics of megestrol acetate in women receiving IM injection of estradiol-megestrol long-acting injectable contraceptive". The Chinese Journal of Clinical Pharmacology. Archived from the original on 2021-05-25. Retrieved 2020-11-25.
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.