Hydroxyprogesterone heptanoate

Hydroxyprogesterone heptanoate
Clinical data
Trade namesH.O.P, Hydroxyprogesterone, Lutogil A.P., Lutogyl A.P., others
Other namesOHPH; Hydroxyprogesterone enanthate; OHPE; 17α-Hydroxyprogesterone heptanoate; 17α-Hydroxyprogesterone heptylate; 17α-Hydroxypregn-4-ene-3,20-dione 17α-heptanoate; 17α-Heptyloylpregn-4-ene-3,20-dione
Routes of
administration		Intramuscular injection
Drug classProgestogen; Progestin; Progestogen ester
ATC code
Identifiers
IUPAC name
  • [(8R,9S,10R,13S,14S,17R)-17-Acetyl-10,13-dimethyl-3-oxo-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-17-yl] heptanoate
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
ECHA InfoCard100.022.724
Edit this at Wikidata
Chemical and physical data
FormulaC28H42O4
Molar mass442.640 g·mol−1
3D model (JSmol)
SMILES
  • CCCCCCC(=O)OC1(CCC2C1(CCC3C2CCC4=CC(=O)CCC34C)C)C(=O)C
InChI
  • InChI=1S/C28H42O4/c1-5-6-7-8-9-25(31)32-28(19(2)29)17-14-24-22-11-10-20-18-21(30)12-15-26(20,3)23(22)13-16-27(24,28)4/h18,22-24H,5-17H2,1-4H3/t22-,23+,24+,26+,27+,28+/m1/s1
  • Key:NKJYZYWCGKSMSV-BDPSOKNUSA-N

Hydroxyprogesterone heptanoate (OHPH), also known as hydroxyprogesterone enanthate (OHPE) and sold under the brand names H.O.P., Lutogil A.P., and Lutogyl A.P. among others, is a progestin medication used for progestogenic indications.[1][2][3][4] It has been formulated both alone and in together with estrogens, androgens/anabolic steroids, and other progestogens in several combination preparations (brand names Tocogestan, Trioestrine Retard, and Triormon Depositum).[4][5][6][7][8][9][10] OHPH is given by injection into muscle at regular intervals.[11][9]

OHPH is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone.[12][13][14] It appears to have similar pharmacology to that of the closely related medication hydroxyprogesterone caproate (OHPC).[15][16][17]

OHPH was first described by 1954[16] and was introduced for medical use by 1957.[6] It has been used clinically in France and Monaco in the past but is no longer marketed.[2][3][4]

Medical uses

OHPH is a progestogen and was used in situations in which progestogens were indicated.[12][13][14]

Available forms

OHPH was provided as a 125 mg/1 mL oil solution for use by intramuscular injection.[3][11] In addition to single-drug preparations, OHPH has also been used in a number of multi-drug formulations.[4][5][6][7][8][9][10] It was used in Tocogestan, a combination of 50 mg progesterone, 200 mg OHPH, and 250 mg α-tocopherol palmitate (vitamin E) in oil solution for use by intramuscular injection.[18][4][5] It was also used in Triormon Depositum (estradiol dibutyrate, testosterone caproate, and OHPH) and Trioestrine Retard (estradiol diundecylate, testosterone cyclohexylpropionate, and OHPH).[6][7] OHPH was a component of the experimental preparation Trophobolene (or Trophoboline), which also contained estrapronicate (estradiol nicotinate propionate) and nandrolone undecanoate, as well.[8][9][10]

Pharmacology

Pharmacodynamics

OHPH is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone.[15][12][13][14] The progestogenic potency of OHPH in the uterus is equal to or greater than that of progesterone when administered by subcutaneous injection in animals.[15][16][17] Its potency in animals likewise appears to be similar to that of hydroxyprogesterone caproate.[15][16][17]

Pharmacokinetics

OHPH shows a pronounced depot effect when administered by subcutaneous injection in animals, similarly to the closely related medication hydroxyprogesterone caproate.[15][16] The oral activity of OHPH in animals does not appear to have been assessed.[15]

Chemistry

OHPH, also known as hydroxyprogesterone enanthate (OHPE),[19] as well as 17α-hydroxyprogesterone heptanoate or 17α-hydroxypregn-4-ene-3,20-dione 17α-heptanoate, is a synthetic pregnane steroid and a derivative of progesterone and 17α-hydroxyprogesterone.[1][2] It is a progestogen ester; specifically, it is the C17α heptanoate (enanthate) ester of 17α-hydroxyprogesterone.[1][2] Analogues of OHPH include the more well-known medications hydroxyprogesterone acetate and hydroxyprogesterone caproate (hydroxyprogesterone hexanoate).[1][2] The C3 benzilic acid hydrazone of OHPH, hydroxyprogesterone heptanoate benzilic acid hydrazone (OHPHBH), is known and has been studied in animals.[20][21] In terms of chemical structure, OHPH is very similar to hydroxyprogesterone caproate, differing from it only in having one additional carbon in its fatty acid ester chain.[1][2]

History

OHPH was first described, along with hydroxyprogesterone caproate and hydroxyprogesterone acetate, by Karl Junkmann of Schering AG in 1954.[16][19] It was introduced for medical use by 1957.[6] OHPH was commercialized by Roussel and Théramex, and has been used clinically in France and Monaco but is no longer marketed.[2][3][4]

Society and culture

Brand names

OHPH has been marketed alone under a number of brand names including H.O.P, Hydroxyprogesterone, Lutogil A.P., and Lutogyl A.P.[1][2][3][4]

Availability

OHPH was previously marketed in France and Monaco but is no longer available.[2][3][22]

See also

References

  1. 1 2 3 4 5 6 J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 665–. ISBN 978-1-4757-2085-3.
  2. 1 2 3 4 5 6 7 8 9 Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 532–. ISBN 978-3-88763-075-1.
  3. 1 2 3 4 5 6 Muller (19 June 1998). European Drug Index: European Drug Registrations, Fourth Edition. CRC Press. pp. 612–. ISBN 978-3-7692-2114-5.
  4. 1 2 3 4 5 6 7 Axel Kleemann; Jürgen Engel (2001). Pharmaceutical Substances: Syntheses, Patents, Applications. Thieme. p. 1033. ISBN 978-3-13-558404-1.
  5. 1 2 3 Sasco AJ, Gendre I, Verbier-Naneix C, Soulier JL, Raffi F, Satgé D, Robert E (1998). "Neonatal neuroblastoma and in utero exposure to progestagens". International Journal of Risk and Safety in Medicine. 11 (2): 121–128.
  6. 1 2 3 4 5 Ermiglia, G; Valli, P (1957). "Triormon depositum in climacteric syndrome. Curves of excretion of catabolites and duration of the therapeutic effect". Quaderni Clin. Ostet. E Ginecol. 12: 284–93. Triormon depositum (estradiol dibutyrate 3, testosterone caprylate 50, and hydroxyprogesterone heptanoate 30 mg.), administered in castor oil-benzyl benzoate soln. or polyvinylpyrrolidone suspension to 21 women in climacteric, was followed by estradiol, pregnanediol, and 17-keto steroid urinary curves, most with a peak at the 4th day, and approaching starting values at the 8-10th day. The therapeutic efficacy of the drug was satisfactory.
  7. 1 2 3 Bordier, Philippe (1963). "Cure of fifteen osteoporosis cases by a delayed effect of hormonal association". Semaine des Hopitaux. 39 (2): 81–4. ISSN 0037-1777. The patients (females) received intramuscularly, every 10 days for 2-3 months, estradiol diundecyleate 2.25, testosterone cyclohexylpropionate 67.5, and hydroxyprogesterone heptylate 100 mg. ("trioestrine retard"). Their av. calcuria decreased 30.5% (0-69%) and asthenia, anorexia, and muscular activity improved.
  8. 1 2 3 Excerpta medica. Section 8, Neurology and neurosurgery. 1981. p. 10.
  9. 1 2 3 4 Testosterone Congeners—Advances in Research and Application: 2013 Edition: ScholarlyBrief. ScholarlyEditions. 21 June 2013. pp. 137–. ISBN 978-1-4816-9288-5.
  10. 1 2 3 Alberto Frigerio (1981). Chromatography in Biochemistry, Medicine and Environmental Research: Proceedings of the ... International Symposium on Chromatography in Biochemistry, Medicine and Environmental Research. Elsevier Scientific Publishing Company. p. 99. ISBN 9780444420169.
  11. 1 2 Leszek Krówczyński (1987). Extended Release Dosage Forms. CRC Press. p. 12. ISBN 978-0-8493-4307-0. Progestogens. [...] Hydroxyprogesterone heptanoate. Hydroxyprogesterone (Theramex). Oily solution for injection.
  12. 1 2 3 Schindler, Adolf E. (2014). "The "newer" progestogens and postmenopausal hormone therapy (HRT)". The Journal of Steroid Biochemistry and Molecular Biology. 142: 48–51. doi:10.1016/j.jsbmb.2013.12.003. ISSN 0960-0760. PMID 24333799. S2CID 32126275.
  13. 1 2 3 Bińkowska, Małgorzata; Woroń, Jarosław (2015). "Progestogens in menopausal hormone therapy". Menopausal Review. 2 (2): 134–143. doi:10.5114/pm.2015.52154. ISSN 1643-8876. PMC 4498031. PMID 26327902.
  14. 1 2 3 Posaci, C.; Smitz, J.; Camus, M.; Osmanagaoglu, K.; Devroey, P. (2000). "Progesterone for the luteal support of assisted reproductive technologies: clinical options". Human Reproduction. 15 (suppl 1): 129–148. doi:10.1093/humrep/15.suppl_1.129. ISSN 0268-1161. PMID 10928425.
  15. 1 2 3 4 5 6 Neumann, F; Elger, W; Salloch, RR; Tube, O; Neumann, HF (1969). "Besonderheiten der Wirkungen der einzelnen Gestagene auf Morphologie und Funktion des Genitaltraktes bei Säugetieren" [Special features of the effects of the individual gestagens on the morphology and function of the genital tract in mammals]. Die Gestagene [Progestogens]. Vol. 2. Springer-Verlag. pp. 50–131. ISBN 978-3-662-00826-3.
  16. 1 2 3 4 5 6 Junkmann K (1954). "Über protrahiert wirksame Gestagene". Naunyn-Schmiedebergs Archiv für Experimentelle Pathologie und Pharmakologie. 223 (3). doi:10.1007/BF00246995. S2CID 33591186.
  17. 1 2 3 Junkmann, K. (1959). Über Entwicklungen auf dem Gestagengebiet. 15. In Meeting Gen. Assembly of the Japan Medical Congr., Tokyo (Vol. 1, pp. 697-706).
  18. ↑ "Formulation".
  19. 1 2 Batres, E.; Gomez, R.; Rosenkranz, G.; Sondheimer, F. (1956). "Notes - Steroids. LXXVI. Synthesis of Long Chain Carboxylic Acid Esters of 17α-Hydroxyprogesterone". The Journal of Organic Chemistry. 21 (2): 240–241. doi:10.1021/jo01108a601. ISSN 0022-3263.
  20. ↑ Ralph I. Dorfman (3 February 2016). Bioassay. Elsevier. pp. 252–. ISBN 978-1-4832-7276-4.
  21. ↑ Gleason CH, Parker JM (1959). "The duration of activity of the benziloyl hydrazones of testosterone-17-heptanoate, estrone-3-heptanoate and 17α-hydroxy-progesterone-17-heptanoate". Endocrinology. 65 (3): 508–511. doi:10.1210/endo-65-3-508. ISSN 0013-7227. PMID 13828402.
  22. ↑ https://www.micromedexsolutions.com/


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