fbpx
Wikipedia

Hydroxyprogesterone acetate

September 01, 2023

Not to be confused with 17α-Hydroxyprogesterone, Hydroxyprogesterone caproate, or Medroxyprogesterone acetate.

Hydroxyprogesterone acetate (OHPA), sold under the brand name Prodox, is an orally active progestin related to hydroxyprogesterone caproate (OHPC) which has been used in clinical and veterinary medicine.[1][2][3][4][5][6][7][8] It has reportedly also been used in birth control pills.[9]

Hydroxyprogesterone acetate
Clinical data
Trade namesProdrox
Other namesOHPA; 17α-Hydroxyprogesterone acetate; 17α-Acetoxyprogesterone; Acetoxyprogesterone; 17α-Hydroxypregn-4-ene-3,20-dione 17α-acetate; 17α-Acetoxypregn-4-ene-3,20-dione
Routes of
administration		By mouth
Drug classProgestogen; Progestin; Progestogen ester
ATC code
Identifiers
  • [(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] acetate
CAS Number
  • 302-23-8
    17308-02-0
PubChem CID
  • 10156152
ChemSpider
  • 8331660
UNII
  • L124O66YSI
KEGG
  • D08053
CompTox Dashboard (EPA)
  • DTXSID90894096
ECHA InfoCard100.005.564
Chemical and physical data
FormulaC23H32O4
Molar mass372.505 g·mol−1
3D model (JSmol)
  • Interactive image
  • O=C4\C=C2/[C@]([C@H]1CC[C@@]3([C@@](OC(=O)C)(C(=O)C)CC[C@H]3[C@@H]1CC2)C)(C)CC4
  • InChI=1S/C23H32O4/c1-14(24)23(27-15(2)25)12-9-20-18-6-5-16-13-17(26)7-10-21(16,3)19(18)8-11-22(20,23)4/h13,18-20H,5-12H2,1-4H3/t18-,19+,20+,21+,22+,23+/m1/s1
  • Key:VTHUYJIXSMGYOQ-KOORYGTMSA-N

OHPA is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone.

OHPA was discovered in 1953 and was introduced for medical use in 1956.[10][11][12]

Medical uses Edit

OHPA has been used in the treatment of a variety of gynecological disorders, including secondary amenorrhea, functional uterine bleeding, infertility, habitual abortion, dysmenorrhea, and premenstrual syndrome.[3][13][14]

OHPA (100 mg) was reportedly marketed in combination with mestranol (80 μg) as a sequential combined birth control pill under the brand name Hormolidin.[9] The preparation was available in the early 1970s.[9] The firm that manufactured it, known as Gador, was based in Argentina.[9]

Available forms Edit

See also: Mestranol/hydroxyprogesterone acetate

Side effects Edit

See also: Progestin § Side effects, and Hydroxyprogesterone caproate § Side effects

Pharmacology Edit

Pharmacodynamics Edit

OHPA is a progestogen and acts as an agonist of the progesterone receptor (PR), both PRA and PRB isoforms (IC50 = 16.8 nM and 12.6 nM, respectively).[15] It has more than 50-fold higher affinity for the PR isoforms than 17α-hydroxyprogesterone, a little less than half the affinity of progesterone, and slightly higher affinity than OHPC.[16] Additional studies have reported on the affinity of OHPA for the PR.[17][18][19][20][21]

OHPA is of relatively low potency as a progestogen, which may explain its relatively limited use.[22] It is 100-fold less potent than medroxyprogesterone acetate, 400-fold less potent than chlormadinone acetate, and 1,200-fold less potent than cyproterone acetate in animal assays.[22] In terms of producing full progestogenic changes on the endometrium in women, 75 to 100 mg/day oral OHPA is equivalent to 20 mg/day parenteral progesterone, and OHPA is at least twice as potent as oral ethisterone in such regards.[3] It is also reportedly more potent than OHPC.[15][23] OHPA has been found to be effective as an oral progestogen-only pill at a dosage of 30 mg/day.[24]

Relative affinities (%) of hydroxyprogesterone and related steroids
Compound hPR-A hPR-B rbPR rbGR rbER
Progesterone 100 100 100 <1 <1
17α-Hydroxyprogesterone 1 1 3 1 <1
Hydroxyprogesterone caproate 26 30 28 4 <1
Hydroxyprogesterone acetate 38 46 115 3 ?
Notes: Values are percentages (%). Reference ligands (100%) were progesterone for the PR, dexamethasone for the GR, and estradiol for the ER. Sources: See template.

Pharmacokinetics Edit

OHPA has very low but nonetheless significant oral bioavailability and can be taken by mouth.[25] The pharmacokinetics of OHPA have been reviewed.[2]

A single intramuscular injection of 150 to 350 mg OHPA in microcrystalline aqueous suspension has been found to have a duration of action of 9 to 16 days in terms of clinical biological effect in the uterus in women.[26]

Parenteral potencies and durations of progestogens[a][b]
Compound Form Dose for specific uses (mg)[c] DOA[d]
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:
  1. ^ Sources: [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45]
  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. ^ a b In divided doses (2 × 125 or 250 mg for OHPC, 10 × 20 mg for P4).

Chemistry Edit

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

OHPA, also known as 17α-hydroxyprogesterone acetate or as 17α-acetoxypregn-4-ene-3,20-dione, is a synthetic pregnane steroid and a derivative of progesterone.[1][46] It is the acetate ester of 17α-hydroxyprogesterone, as well as a parent compound of a number of progestins including chlormadinone acetate, cyproterone acetate, medroxyprogesterone acetate, and megestrol acetate.[4][46]

Synthesis Edit

Chemical syntheses of OHPA have been described.[2]

History Edit

In 1949, it was discovered that 17α-methylprogesterone had twice the progestogenic activity of progesterone when administered parenterally,[47] and this finding led to renewed interest in 17α-substituted derivatives of progesterone as potential progestins.[12] Along with OHPC, OHPA was synthesized by Karl Junkmann of Schering AG in 1953 and was first reported by him in the medical literature in 1954.[10][11][48][49][12] OHPC shows very low oral activity[16] and was introduced for use via intramuscular injection by Squibb in 1956 under the brand name Delalutin.[12] Although a substantial prolongation of action occurs when OHPC is formulated in oil,[16] the same was not observed to a significant extent with OHPA, and this is likely why OHPC was chosen by Schering for development over OHPA.[7]

Subsequently, Upjohn unexpectedly discovered that OHPA, unlike OHPC and progesterone, is orally active and shows marked progestogenic activity with oral administration,[25] a finding that had been missed by the Schering researchers (who were primarily interested in the oil solubility of such esters).[7][12] OHPA was found to possess two to three times the oral activity of 17α-methylprogesterone.[50] Upjohn reported the oral activity of OHPA in the medical literature in 1957 and introduced the drug for medical use as Prodox in 25 mg and 50 mg oral tablet formulations later the same year.[3][12][13] OHPA was indicated for the treatment of a variety of gynecological disorders in women.[3][13][14] However, it saw relatively little use, which was perhaps due its comparatively low potency relative to a variety of other progestins such as medroxyprogesterone acetate and norethisterone.[22][14] These progestins were introduced around the same time and hence may have been favored.[22][14]

In 1960, OHPA was introduced also as Prodox as an oral progestin for veterinary use for the indication of estrus suppression in dogs.[8][51] However, probably due its high cost and the inconvenience of daily oral administration, the drug was not a market success.[8] It was superseded for this indication by medroxyprogesterone acetate (brand name Promone) in 1963, which could be administered by injection conveniently once every six months, although this preparation was discontinued in 1966 for various reasons and hence was not a market success either.[8]

Society and culture Edit

Generic names Edit

Hydroxyprogesterone acetate is the generic name of the drug and its INN.[1]

Brand names Edit

OHPA is or was marketed under the brand name Prodox initially for clinical use and then for veterinary use.[1] Other brand names of OHPA include Gestageno, Gestageno Gador, Kyormon, Lutate-Inj, Prodix, and Prokan.[1] OHPA may also be or have been marketed in combination with estradiol enantate under the brand names Atrimon and Protegin in Argentina and Nicaragua.[52]

Availability Edit

OHPA is no longer marketed and hence is no longer available in any country.[53][54][52]

See also Edit

References Edit

  1. ^ a b c d e Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 664–. ISBN 978-1-4757-2085-3.
  2. ^ a b c Junkmann K (27 November 2013). "Konstitution und chemische und physikalische Eigenschaften der Gestagene" [Constitution and chemical and physical properties of progestogens]. Die Gestagene (in German). Springer-Verlag. pp. 6, 278. ISBN 978-3-642-99941-3.
  3. ^ a b c d e Davis ME, Wied GL (1957). "17-alpha-HYDROXYPROGESTERONE acetate; an effective progestational substance on oral administration". The Journal of Clinical Endocrinology and Metabolism. 17 (10): 1237–44. doi:10.1210/jcem-17-10-1237. PMID 13475464. It is the purpose of this paper to introduce and describe a new steroid for oral administration, 17-a-hydroxyprogesterone acetate*, and to compare it with the most widely used oral substance with progestational properties, 20,21-anhydro-17-/3-hydroxyprogesterone. * Prodox, Upjohn Co., Kalamazoo, Michigan [...] It was found that 17-a-hydroxyprogesterone acetate has a progestational activity which is at least twice that of anhydrohydroxyprogesterone.
  4. ^ a b Lobo R, Crosignani PG, Paoletti R (31 October 2002). Women's Health and Menopause: New Strategies - Improved Quality of Life. Springer Science & Business Media. pp. 91–. ISBN 978-1-4020-7149-2.
  5. ^ Stoller JK, Michota FA, Mandell BF (2009). The Cleveland Clinic Foundation Intensive Review of Internal Medicine. Lippincott Williams & Wilkins. pp. 13–. ISBN 978-0-7817-9079-6.
  6. ^ Ravina E (11 January 2011). "Hormone Analogs". The Evolution of Drug Discovery: From Traditional Medicines to Modern Drugs. John Wiley & Sons. pp. 194–. ISBN 978-3-527-32669-3.
  7. ^ a b c Sneader W (23 June 2005). Drug Discovery: A History. John Wiley & Sons. pp. 204–. ISBN 978-0-471-89979-2. In 1954, Karl Junkmann of Schering AG reported that the acetylation of the 17-hydroxyl group of ethisterone provided a derivative suitable for formulating in oil for injection intramuscularly as a depot medication.79 There resulted widespread interest in preparing the acetates (and other esters) of various hydroxy-steroids. One such ester, Upjohn's 17-acetoxyprogesterone, provided to be a promising progestogen even though its hydroxy precursor was inactive. Unfortunately, it turned out that no significant prolongation of action was obtained by formulating it in oil. The Upjohn researchers, however, made the unexpected discovery that their acetoxy derivative was orally active, an observation that had been missed by the Schering group, who were primarily interested in the oil solubility of such esters.
  8. ^ a b c d Lauderdale JW, Sokolowski JH, eds. (1978). Proceedings of the Symposium on Cheque® for Canine Estrus Prevention, Brook Lodge, Augusta, Michigan, March 13-15, 1978. Upjohn Company. p. 16. [...] The first product was 17alpha-acetoxyprogesterone4 (Figure 1) marketed under the trade name of Prodox.® Prodox was introduced in 1960, was designed for oral use and was not a marketing success. The reasons are not clear as to lack of clear success, but one predominant reason was the high cost. For the average size dog, the cost of preventing estrus for a year was approximately $90. In addition, the inconvenience of daily oral administration may have prevented some market acceptance, especially at that cost. In 1963, Upjohn introduced injectable medroxyprogesterone acetate6 (Figure 1) under the trade name of Promone. Injections were to be made every six months, and this procedure was well accepted by both veterinarians and pet owners. However, Promone sales were discontinued in April, 1966 in the United States for basically two reasons. First was a prolonged and unpredictable return to estrus. This appeared to be due to very slow and variable absorption from the injection site. As a result of this variable absorption rate, one would expect a variable return to estrus. Even after [...]
  9. ^ a b c d Rudel HW, Kinel FA (September 1972). "Oral Contraceptives. Human Fertility Studies and Side Effects". In Tausk M (ed.). Pharmacology of the Endocrine System and Related Drugs: Progesterone, Progestational Drugs and Antifertility Agents. Vol. II. Pergamon Press. pp. 385–469. ISBN 978-0080168128. OCLC 278011135.
  10. ^ a b Davis ME (1930). M. Edward Davis Reprints. p. 406. Chemically pure progesterone was the only substance with progestational properties in general use which could be administered parenterally until Junkmann (1) developed in 1953, 17-alpha-hydroxyprogesterone acetate and 17-alpha-hydroxyprogesterone caproate.
  11. ^ a b Wied GL, Davis ME (1958). "Comparative activity of progestational agents on the human endometrium and vaginal epithelium of surgical castrates". Ann. N. Y. Acad. Sci. 71 (5): 599–616. Bibcode:1958NYASA..71..599W. doi:10.1111/j.1749-6632.1958.tb46791.x. PMID 13583817. In the group of new parenteral progestational agents, three substances developed by Karl Junkmann1,2 are the most outstanding and interesting: 17a-hydroxyprogesterone caproate and 17a-hydroxyprogesterone acetate, introduced in 1953, and the most potent of all new parenteral progestational agents, 17-ethynyl-19-nortestosterone enanthate, introduced in 1956.
  12. ^ a b c d e f Applezweig N (1962). Steroid Drugs. Blakiston Division, McGraw-Hill. pp. 101–102. Junkmann of Schering, AG., however, was able to show that long chain esters of 17a-hydroxyprogesterones such as the 17a-caproate produced powerful long-acting progestational effect. [...] Subsequently, a series of events led to the exploitation of 17a-hydroxyprogesterone derivatives as highly effective and orally active progestogens. Groups at Upjohn, Merck & Co., and Syntex independently found means of readily acetylating the 17-hydroxy group. Later, Upjohn announced it found that 17a-acetoxyprogesterone was orally active in humans and subsequently marketed this compound under the name of Prodox.
  13. ^ a b c Medical Digest. Medical Digest. Incorporated. 1958. Prodox Tablets ( Upjohn) A new derivative of progesterone for oral administration. Indications: Secondary amenorrhea, functional uterine bleeding, in- fertility, habitual abortion, dysmen-orrhea and premenstrual tension. Supplied: Tablets containing 25 mg. or 50 mg. of hydroxyprogesterone a c e t a te, in bottles of 25 tablets.
  14. ^ a b c d Greenblatt RB (1959). "Hormonal control of functional uterine bleeding". Clinical Obstetrics and Gynecology. 2 (1): 232–46. doi:10.1097/00003081-195903000-00021. PMID 13639329. [...] ethisterone, 25 mg. (Lutocylol; Pranone) 17-acetoxyprogesterone, 25 mg. (Prodox), 6-methyl-17-acetoxyprogesterone, 5 mg. (Provera), norethindrone, 5 mg. (Norlutin), norethinodrel, 5 mg. (Enovid). [...]
  15. ^ a b Attardi BJ, Zeleznik A, Simhan H, Chiao JP, Mattison DR, Caritis SN (2007). "Comparison of progesterone and glucocorticoid receptor binding and stimulation of gene expression by progesterone, 17-alpha hydroxyprogesterone caproate, and related progestins". American Journal of Obstetrics and Gynecology. 197 (6): 599.e1–7. doi:10.1016/j.ajog.2007.05.024. PMC 2278032. PMID 18060946.
  16. ^ a b c Shaik IH, Bastian JR, Zhao Y, Caritis SN, Venkataramanan R (2015). "Route of administration and formulation dependent pharmacokinetics of 17-hydroxyprogesterone caproate in rats". Xenobiotica; The Fate of Foreign Compounds in Biological Systems. 46 (2): 169–174. doi:10.3109/00498254.2015.1057547. PMC 4809632. PMID 26153441.
  17. ^ Lontula K, Luukkainen JT, Vihko R (November 1973). "Progesterone-binding protein in human myometrium. Ligand specificity and some physicochemical characteristics". Biochim. Biophys. Acta. 328 (1): 145–53. doi:10.1016/0005-2795(73)90340-1. PMID 4357561.
  18. ^ McGuire JL, Bariso CD, Shroff AP (January 1974). "Interaction between steroids and a uterine progestogen specific binding macromolecule". Biochemistry. 13 (2): 319–22. doi:10.1021/bi00699a014. PMID 4129556.
  19. ^ Smith HE, Smith RG, Toft DO, Neergaard JR, Burrows EP, O'Malley BW (September 1974). "Binding of steroids to progesterone receptor proteins in chick oviduct and human uterus". J. Biol. Chem. 249 (18): 5924–32. doi:10.1016/S0021-9258(20)79907-2. PMID 4369808.
  20. ^ Blanford AT, Wittman W, Stroupes SD, Westphal U (March 1978). "Steroid--protein interactions--XXXVIII. Influence of steroid structure on affinity to the progesterone-binding globulin". J. Steroid Biochem. 9 (3): 187–201. doi:10.1016/0022-4731(78)90149-8. PMID 77359.
  21. ^ Wilks JW, Spilman CH, Campbell JA (June 1980). "Steroid binding specificity of the hamster uterine progesterone receptor". Steroids. 35 (6): 697–706. doi:10.1016/0039-128x(80)90094-x. PMID 7404605. S2CID 5895412.
  22. ^ a b c d Neumann F, Düsterberg B, Laurent H (6 December 2012). "Development of progestogens". In Runnebaum BC, Rabe T, Kiesel L (eds.). Female Contraception: Update and Trends. Springer Science & Business Media. pp. 133–134. ISBN 978-3-642-73790-9.
  23. ^ Barnes AC (1961). Progesterone. Brook Lodge Press. p. 28. Hydroxyprogesterone cap- roate appears to be even less active than Prodox in some respects. It is about 5 times progesterone as an endometrial stimulator [...]
  24. ^ Lönnerdal B (6 December 2012). "Effect of Oral Contraceptives on Lactation". In Hamosh M, Goldman AS (eds.). Human Lactation 2: Maternal and Environmental Factors. Springer Science & Business Media. pp. 454–. ISBN 978-1-4615-7207-7.
  25. ^ a b Veterinary Medicine. 1959. p. 152. Whereas progesterone is relatively inactive when administered orally, ethisterone (anhydrohydroxyprogesterone) and hydroxyprogesterone acetate are highly active.
  26. ^ 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.
  27. ^ Knörr K, Beller FK, Lauritzen C (17 April 2013). Lehrbuch der Gynäkologie. Springer-Verlag. pp. 214–. ISBN 978-3-662-00942-0.
  28. ^ 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.
  29. ^ Labhart A (6 December 2012). Clinical Endocrinology: Theory and Practice. Springer Science & Business Media. pp. 554–. ISBN 978-3-642-96158-8.
  30. ^ 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. Springer Science & Business Media. pp. 309–332. doi:10.1007/978-94-009-8195-9_11. ISBN 978-94-009-8195-9.
  31. ^ 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.
  32. ^ Pschyrembel W (1968). Praktische Gynäkologie: für Studierende und Ärzte. Walter de Gruyter. pp. 598, 601. ISBN 978-3-11-150424-7.
  33. ^ 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.
  34. ^ 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.
  35. ^ Brotherton J (1976). Sex Hormone Pharmacology. Academic Press. p. 114. ISBN 978-0-12-137250-7.
  36. ^ Sang GW (April 1994). "Pharmacodynamic effects of once-a-month combined injectable contraceptives". Contraception. 49 (4): 361–385. doi:10.1016/0010-7824(94)90033-7. PMID 8013220.
  37. ^ 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.
  38. ^ Goebelsmann U (1986). "Pharmacokinetics of Contraceptive Steroids in Humans". In Gregoire AT, Blye RP (eds.). Contraceptive Steroids: Pharmacology and Safety. Springer Science & Business Media. pp. 67–111. doi:10.1007/978-1-4613-2241-2_4. ISBN 978-1-4613-2241-2.
  39. ^ 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): 381–385. doi:10.1159/000280353. PMID 6452729.
  40. ^ 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): 281–287. doi:10.1055/s-2008-1036893. PMID 6223851.
  41. ^ Wright JC, Burgess DJ (29 January 2012). Long Acting Injections and Implants. Springer Science & Business Media. pp. 114–. ISBN 978-1-4614-0554-2.
  42. ^ 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. 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.
  43. ^ 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.
  44. ^ Artini PG, Genazzani AR, Petraglia F (11 December 2001). Advances in Gynecological Endocrinology. CRC Press. pp. 105–. ISBN 978-1-84214-071-0.
  45. ^ 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.
  46. ^ a b Jurow R, Shoupe D (7 November 2007). "Long-Acting Progestin Injectables: Comparison ofDepo-Provera With Depo-SubQProvera 104". In Shoupe D, Kjos SL (eds.). The Handbook of Contraception: A Guide for Practical Management. Springer Science & Business Media. pp. 103–. ISBN 978-1-59745-150-5.
  47. ^ Plattner PA, Heusser H, Herzig PT (1949). "Uber steroide und sexualhormone. 159. Die synthese von 17-methyl-progesteron". Helvetica Chimica Acta. 32 (1): 270–275. doi:10.1002/hlca.19490320138. PMID 18115956.
  48. ^ ACRH. U.S. Dept. of Energy. 1960. p. 71. [The] minimal activity [of 17(a)-hydroxyprogesterone] is magnified to an unexpected degree by the esterification of this steroid with caproic acid to produce 17(a)-hydroxyprogesterone-17-n-caproate, first reported by Karl Junkmann in 1954.6,7
  49. ^ Dorfman RI (1966). Methods in Hormone Research. Academic Press. p. 86. Junkmann (1954) reported that the acetate, butyrate, and caproate forms had both increased and prolonged activity, [...]
  50. ^ Kirk RE, Othmer DF, Mark HF (1965). Encyclopedia of chemical technology. Interscience Publishers. p. 78. Subsequent acetylation with acetic anhydride and tosyl acid followed by Oppenauer oxidation afforded 17a-acetoxy- progesterone (95) in good yield (115). Tests showed this compound to possess 2-3 times the oral activity of 17-methylpregn-4-ene-3,20-dione (78) and to be many times more potent than progesterone (116,117).
  51. ^ Pure-bred Dogs, American Kennel Gazette. American Kennel Club. 1961. p. 33. According to Dr. Gordon G. Stocking, director of Upjohn's Veterinary Division, Prodox is a synthetic version of progesterone — one of the hormones that regulates the human female reproductive system. It is 100 per cent effective and has produced no ill-effects on 200 or more dogs on which it has been tested. As a result of its findings, says Dr. Stocking, Upjohn is making the product available through veterinarians.
  52. ^ a b "Hydroxyprogesterone injection Uses, Side Effects & Warnings".
  53. ^ Index Nominum 2000: International Drug Directory. Taylor & Francis. 2000. pp. 532–. ISBN 978-3-88763-075-1.
  54. ^ Sweetman SC, ed. (2009). "Sex hormones and their modulators". Martindale: The Complete Drug Reference (36th ed.). London: Pharmaceutical Press. p. 2110. ISBN 978-0-85369-840-1.


September 01, 2023
hydroxyprogesterone, acetate, confused, with, 17α, hydroxyprogesterone, hydroxyprogesterone, caproate, medroxyprogesterone, acetate, ohpa, sold, under, brand, name, prodox, orally, active, progestin, related, hydroxyprogesterone, caproate, ohpc, which, been, u. Not to be confused with 17a Hydroxyprogesterone Hydroxyprogesterone caproate or Medroxyprogesterone acetate Hydroxyprogesterone acetate OHPA sold under the brand name Prodox is an orally active progestin related to hydroxyprogesterone caproate OHPC which has been used in clinical and veterinary medicine 1 2 3 4 5 6 7 8 It has reportedly also been used in birth control pills 9 Hydroxyprogesterone acetateClinical dataTrade namesProdroxOther namesOHPA 17a Hydroxyprogesterone acetate 17a Acetoxyprogesterone Acetoxyprogesterone 17a Hydroxypregn 4 ene 3 20 dione 17a acetate 17a Acetoxypregn 4 ene 3 20 dioneRoutes ofadministrationBy mouthDrug classProgestogen Progestin Progestogen esterATC codeG03DA03 WHO IdentifiersIUPAC 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 acetateCAS Number302 23 8 17308 02 0PubChem CID10156152ChemSpider8331660UNIIL124O66YSIKEGGD08053CompTox Dashboard EPA DTXSID90894096ECHA InfoCard100 005 564Chemical and physical dataFormulaC 23H 32O 4Molar mass372 505 g mol 13D model JSmol Interactive imageSMILES O C4 C C2 C C H 1CC C 3 C OC O C C O C CC C H 3 C H 1CC2 C C CC4InChI InChI 1S C23H32O4 c1 14 24 23 27 15 2 25 12 9 20 18 6 5 16 13 17 26 7 10 21 16 3 19 18 8 11 22 20 23 4 h13 18 20H 5 12H2 1 4H3 t18 19 20 21 22 23 m1 s1Key VTHUYJIXSMGYOQ KOORYGTMSA NOHPA is a progestin or a synthetic progestogen and hence is an agonist of the progesterone receptor the biological target of progestogens like progesterone OHPA was discovered in 1953 and was introduced for medical use in 1956 10 11 12 Contents 1 Medical uses 1 1 Available forms 2 Side effects 3 Pharmacology 3 1 Pharmacodynamics 3 2 Pharmacokinetics 4 Chemistry 4 1 Synthesis 5 History 6 Society and culture 6 1 Generic names 6 2 Brand names 6 3 Availability 7 See also 8 ReferencesMedical uses EditOHPA has been used in the treatment of a variety of gynecological disorders including secondary amenorrhea functional uterine bleeding infertility habitual abortion dysmenorrhea and premenstrual syndrome 3 13 14 OHPA 100 mg was reportedly marketed in combination with mestranol 80 mg as a sequential combined birth control pill under the brand name Hormolidin 9 The preparation was available in the early 1970s 9 The firm that manufactured it known as Gador was based in Argentina 9 Available forms Edit See also Mestranol hydroxyprogesterone acetateSide effects EditSee also Progestin Side effects and Hydroxyprogesterone caproate Side effectsPharmacology EditPharmacodynamics Edit OHPA is a progestogen and acts as an agonist of the progesterone receptor PR both PRA and PRB isoforms IC50 16 8 nM and 12 6 nM respectively 15 It has more than 50 fold higher affinity for the PR isoforms than 17a hydroxyprogesterone a little less than half the affinity of progesterone and slightly higher affinity than OHPC 16 Additional studies have reported on the affinity of OHPA for the PR 17 18 19 20 21 OHPA is of relatively low potency as a progestogen which may explain its relatively limited use 22 It is 100 fold less potent than medroxyprogesterone acetate 400 fold less potent than chlormadinone acetate and 1 200 fold less potent than cyproterone acetate in animal assays 22 In terms of producing full progestogenic changes on the endometrium in women 75 to 100 mg day oral OHPA is equivalent to 20 mg day parenteral progesterone and OHPA is at least twice as potent as oral ethisterone in such regards 3 It is also reportedly more potent than OHPC 15 23 OHPA has been found to be effective as an oral progestogen only pill at a dosage of 30 mg day 24 vte Relative affinities of hydroxyprogesterone and related steroids Compound hPR A hPR B rbPR rbGR rbERProgesterone 100 100 100 lt 1 lt 117a Hydroxyprogesterone 1 1 3 1 lt 1Hydroxyprogesterone caproate 26 30 28 4 lt 1Hydroxyprogesterone acetate 38 46 115 3 Notes Values are percentages Reference ligands 100 were progesterone for the PR dexamethasone for the GR and estradiol for the ER Sources See template Pharmacokinetics Edit OHPA has very low but nonetheless significant oral bioavailability and can be taken by mouth 25 The pharmacokinetics of OHPA have been reviewed 2 A single intramuscular injection of 150 to 350 mg OHPA in microcrystalline aqueous suspension has been found to have a duration of action of 9 to 16 days in terms of clinical biological effect in the uterus in women 26 vte Parenteral potencies and durations of progestogens a b Compound Form Dose for specific uses mg c DOA d TFD e POICD f CICD g Algestone acetophenide Oil soln 75 150 14 32 dGestonorone caproate Oil soln 25 50 8 13 dHydroxyprogest acetate h Aq susp 350 9 16 dHydroxyprogest caproate Oil soln 250 500 i 250 500 5 21 dMedroxyprog acetate Aq susp 50 100 150 25 14 50 dMegestrol acetate Aq susp 25 gt 14 dNorethisterone enanthate Oil soln 100 200 200 50 11 52 dProgesterone Oil soln 200 i 2 6 dAq soln 1 2 dAq susp 50 200 7 14 dNotes and sources Sources 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 All given by intramuscular or subcutaneous injection Progesterone production during the luteal phase is 25 15 50 mg day The OID of OHPC is 250 to 500 mg month Duration of action in days Usually given for 14 days Usually dosed every two to three months Usually dosed once monthly Never marketed or approved by this route a b In divided doses 2 125 or 250 mg for OHPC 10 20 mg for P4 Chemistry EditSee also List of progestogens Progestogen ester and List of progestogen esters OHPA also known as 17a hydroxyprogesterone acetate or as 17a acetoxypregn 4 ene 3 20 dione is a synthetic pregnane steroid and a derivative of progesterone 1 46 It is the acetate ester of 17a hydroxyprogesterone as well as a parent compound of a number of progestins including chlormadinone acetate cyproterone acetate medroxyprogesterone acetate and megestrol acetate 4 46 Synthesis Edit Chemical syntheses of OHPA have been described 2 History EditIn 1949 it was discovered that 17a methylprogesterone had twice the progestogenic activity of progesterone when administered parenterally 47 and this finding led to renewed interest in 17a substituted derivatives of progesterone as potential progestins 12 Along with OHPC OHPA was synthesized by Karl Junkmann of Schering AG in 1953 and was first reported by him in the medical literature in 1954 10 11 48 49 12 OHPC shows very low oral activity 16 and was introduced for use via intramuscular injection by Squibb in 1956 under the brand name Delalutin 12 Although a substantial prolongation of action occurs when OHPC is formulated in oil 16 the same was not observed to a significant extent with OHPA and this is likely why OHPC was chosen by Schering for development over OHPA 7 Subsequently Upjohn unexpectedly discovered that OHPA unlike OHPC and progesterone is orally active and shows marked progestogenic activity with oral administration 25 a finding that had been missed by the Schering researchers who were primarily interested in the oil solubility of such esters 7 12 OHPA was found to possess two to three times the oral activity of 17a methylprogesterone 50 Upjohn reported the oral activity of OHPA in the medical literature in 1957 and introduced the drug for medical use as Prodox in 25 mg and 50 mg oral tablet formulations later the same year 3 12 13 OHPA was indicated for the treatment of a variety of gynecological disorders in women 3 13 14 However it saw relatively little use which was perhaps due its comparatively low potency relative to a variety of other progestins such as medroxyprogesterone acetate and norethisterone 22 14 These progestins were introduced around the same time and hence may have been favored 22 14 In 1960 OHPA was introduced also as Prodox as an oral progestin for veterinary use for the indication of estrus suppression in dogs 8 51 However probably due its high cost and the inconvenience of daily oral administration the drug was not a market success 8 It was superseded for this indication by medroxyprogesterone acetate brand name Promone in 1963 which could be administered by injection conveniently once every six months although this preparation was discontinued in 1966 for various reasons and hence was not a market success either 8 Society and culture EditGeneric names Edit Hydroxyprogesterone acetate is the generic name of the drug and its INN 1 Brand names Edit OHPA is or was marketed under the brand name Prodox initially for clinical use and then for veterinary use 1 Other brand names of OHPA include Gestageno Gestageno Gador Kyormon Lutate Inj Prodix and Prokan 1 OHPA may also be or have been marketed in combination with estradiol enantate under the brand names Atrimon and Protegin in Argentina and Nicaragua 52 Availability Edit OHPA is no longer marketed and hence is no longer available in any country 53 54 52 See also EditMestranol hydroxyprogesterone acetateReferences Edit a b c d e Elks J 14 November 2014 The Dictionary of Drugs Chemical Data Chemical Data Structures and Bibliographies Springer pp 664 ISBN 978 1 4757 2085 3 a b c Junkmann K 27 November 2013 Konstitution und chemische und physikalische Eigenschaften der Gestagene Constitution and chemical and physical properties of progestogens Die Gestagene in German Springer Verlag pp 6 278 ISBN 978 3 642 99941 3 a b c d e Davis ME Wied GL 1957 17 alpha HYDROXYPROGESTERONE acetate an effective progestational substance on oral administration The Journal of Clinical Endocrinology and Metabolism 17 10 1237 44 doi 10 1210 jcem 17 10 1237 PMID 13475464 It is the purpose of this paper to introduce and describe a new steroid for oral administration 17 a hydroxyprogesterone acetate and to compare it with the most widely used oral substance with progestational properties 20 21 anhydro 17 3 hydroxyprogesterone Prodox Upjohn Co Kalamazoo Michigan It was found that 17 a hydroxyprogesterone acetate has a progestational activity which is at least twice that of anhydrohydroxyprogesterone a b Lobo R Crosignani PG Paoletti R 31 October 2002 Women s Health and Menopause New Strategies Improved Quality of Life Springer Science amp Business Media pp 91 ISBN 978 1 4020 7149 2 Stoller JK Michota FA Mandell BF 2009 The Cleveland Clinic Foundation Intensive Review of Internal Medicine Lippincott Williams amp Wilkins pp 13 ISBN 978 0 7817 9079 6 Ravina E 11 January 2011 Hormone Analogs The Evolution of Drug Discovery From Traditional Medicines to Modern Drugs John Wiley amp Sons pp 194 ISBN 978 3 527 32669 3 a b c Sneader W 23 June 2005 Drug Discovery A History John Wiley amp Sons pp 204 ISBN 978 0 471 89979 2 In 1954 Karl Junkmann of Schering AG reported that the acetylation of the 17 hydroxyl group of ethisterone provided a derivative suitable for formulating in oil for injection intramuscularly as a depot medication 79 There resulted widespread interest in preparing the acetates and other esters of various hydroxy steroids One such ester Upjohn s 17 acetoxyprogesterone provided to be a promising progestogen even though its hydroxy precursor was inactive Unfortunately it turned out that no significant prolongation of action was obtained by formulating it in oil The Upjohn researchers however made the unexpected discovery that their acetoxy derivative was orally active an observation that had been missed by the Schering group who were primarily interested in the oil solubility of such esters a b c d Lauderdale JW Sokolowski JH eds 1978 Proceedings of the Symposium on Cheque for Canine Estrus Prevention Brook Lodge Augusta Michigan March 13 15 1978 Upjohn Company p 16 The first product was 17alpha acetoxyprogesterone4 Figure 1 marketed under the trade name of Prodox Prodox was introduced in 1960 was designed for oral use and was not a marketing success The reasons are not clear as to lack of clear success but one predominant reason was the high cost For the average size dog the cost of preventing estrus for a year was approximately 90 In addition the inconvenience of daily oral administration may have prevented some market acceptance especially at that cost In 1963 Upjohn introduced injectable medroxyprogesterone acetate6 Figure 1 under the trade name of Promone Injections were to be made every six months and this procedure was well accepted by both veterinarians and pet owners However Promone sales were discontinued in April 1966 in the United States for basically two reasons First was a prolonged and unpredictable return to estrus This appeared to be due to very slow and variable absorption from the injection site As a result of this variable absorption rate one would expect a variable return to estrus Even after a b c d Rudel HW Kinel FA September 1972 Oral Contraceptives Human Fertility Studies and Side Effects In Tausk M ed Pharmacology of the Endocrine System and Related Drugs Progesterone Progestational Drugs and Antifertility Agents Vol II Pergamon Press pp 385 469 ISBN 978 0080168128 OCLC 278011135 a b Davis ME 1930 M Edward Davis Reprints p 406 Chemically pure progesterone was the only substance with progestational properties in general use which could be administered parenterally until Junkmann 1 developed in 1953 17 alpha hydroxyprogesterone acetate and 17 alpha hydroxyprogesterone caproate a b Wied GL Davis ME 1958 Comparative activity of progestational agents on the human endometrium and vaginal epithelium of surgical castrates Ann N Y Acad Sci 71 5 599 616 Bibcode 1958NYASA 71 599W doi 10 1111 j 1749 6632 1958 tb46791 x PMID 13583817 In the group of new parenteral progestational agents three substances developed by Karl Junkmann1 2 are the most outstanding and interesting 17a hydroxyprogesterone caproate and 17a hydroxyprogesterone acetate introduced in 1953 and the most potent of all new parenteral progestational agents 17 ethynyl 19 nortestosterone enanthate introduced in 1956 a b c d e f Applezweig N 1962 Steroid Drugs Blakiston Division McGraw Hill pp 101 102 Junkmann of Schering AG however was able to show that long chain esters of 17a hydroxyprogesterones such as the 17a caproate produced powerful long acting progestational effect Subsequently a series of events led to the exploitation of 17a hydroxyprogesterone derivatives as highly effective and orally active progestogens Groups at Upjohn Merck amp Co and Syntex independently found means of readily acetylating the 17 hydroxy group Later Upjohn announced it found that 17a acetoxyprogesterone was orally active in humans and subsequently marketed this compound under the name of Prodox a b c Medical Digest Medical Digest Incorporated 1958 Prodox Tablets Upjohn A new derivative of progesterone for oral administration Indications Secondary amenorrhea functional uterine bleeding in fertility habitual abortion dysmen orrhea and premenstrual tension Supplied Tablets containing 25 mg or 50 mg of hydroxyprogesterone a c e t a te in bottles of 25 tablets a b c d Greenblatt RB 1959 Hormonal control of functional uterine bleeding Clinical Obstetrics and Gynecology 2 1 232 46 doi 10 1097 00003081 195903000 00021 PMID 13639329 ethisterone 25 mg Lutocylol Pranone 17 acetoxyprogesterone 25 mg Prodox 6 methyl 17 acetoxyprogesterone 5 mg Provera norethindrone 5 mg Norlutin norethinodrel 5 mg Enovid a b Attardi BJ Zeleznik A Simhan H Chiao JP Mattison DR Caritis SN 2007 Comparison of progesterone and glucocorticoid receptor binding and stimulation of gene expression by progesterone 17 alpha hydroxyprogesterone caproate and related progestins American Journal of Obstetrics and Gynecology 197 6 599 e1 7 doi 10 1016 j ajog 2007 05 024 PMC 2278032 PMID 18060946 a b c Shaik IH Bastian JR Zhao Y Caritis SN Venkataramanan R 2015 Route of administration and formulation dependent pharmacokinetics of 17 hydroxyprogesterone caproate in rats Xenobiotica The Fate of Foreign Compounds in Biological Systems 46 2 169 174 doi 10 3109 00498254 2015 1057547 PMC 4809632 PMID 26153441 Lontula K Luukkainen JT Vihko R November 1973 Progesterone binding protein in human myometrium Ligand specificity and some physicochemical characteristics Biochim Biophys Acta 328 1 145 53 doi 10 1016 0005 2795 73 90340 1 PMID 4357561 McGuire JL Bariso CD Shroff AP January 1974 Interaction between steroids and a uterine progestogen specific binding macromolecule Biochemistry 13 2 319 22 doi 10 1021 bi00699a014 PMID 4129556 Smith HE Smith RG Toft DO Neergaard JR Burrows EP O Malley BW September 1974 Binding of steroids to progesterone receptor proteins in chick oviduct and human uterus J Biol Chem 249 18 5924 32 doi 10 1016 S0021 9258 20 79907 2 PMID 4369808 Blanford AT Wittman W Stroupes SD Westphal U March 1978 Steroid protein interactions XXXVIII Influence of steroid structure on affinity to the progesterone binding globulin J Steroid Biochem 9 3 187 201 doi 10 1016 0022 4731 78 90149 8 PMID 77359 Wilks JW Spilman CH Campbell JA June 1980 Steroid binding specificity of the hamster uterine progesterone receptor Steroids 35 6 697 706 doi 10 1016 0039 128x 80 90094 x PMID 7404605 S2CID 5895412 a b c d Neumann F Dusterberg B Laurent H 6 December 2012 Development of progestogens In Runnebaum BC Rabe T Kiesel L eds Female Contraception Update and Trends Springer Science amp Business Media pp 133 134 ISBN 978 3 642 73790 9 Barnes AC 1961 Progesterone Brook Lodge Press p 28 Hydroxyprogesterone cap roate appears to be even less active than Prodox in some respects It is about 5 times progesterone as an endometrial stimulator Lonnerdal B 6 December 2012 Effect of Oral Contraceptives on Lactation In Hamosh M Goldman AS eds Human Lactation 2 Maternal and Environmental Factors Springer Science amp Business Media pp 454 ISBN 978 1 4615 7207 7 a b Veterinary Medicine 1959 p 152 Whereas progesterone is relatively inactive when administered orally ethisterone anhydrohydroxyprogesterone and hydroxyprogesterone acetate are highly active 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 Knorr K Beller FK Lauritzen C 17 April 2013 Lehrbuch der Gynakologie Springer Verlag pp 214 ISBN 978 3 662 00942 0 Knorr K Knorr Gartner H Beller FK Lauritzen C 8 March 2013 Geburtshilfe und Gynakologie 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 amp Business Media pp 554 ISBN 978 3 642 96158 8 Horsky 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 Springer Science amp 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 17a 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 Gynakologie fur Studierende und Arzte 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 17a Hydroxyprogesterone Derivatives and Progestins of the First and Second Generation In Sitruk Ware R Mishell DR eds Progestins and Antiprogestins in Clinical Practice Taylor amp 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 4 361 385 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 Goebelsmann U 1986 Pharmacokinetics of Contraceptive Steroids in Humans In Gregoire AT Blye RP eds Contraceptive Steroids Pharmacology and Safety Springer Science amp Business Media pp 67 111 doi 10 1007 978 1 4613 2241 2 4 ISBN 978 1 4613 2241 2 Becker H Dusterberg 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 6 381 385 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 5 281 287 doi 10 1055 s 2008 1036893 PMID 6223851 Wright JC Burgess DJ 29 January 2012 Long Acting Injections and Implants Springer Science amp 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 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 2b 14 35 9 1 days Runnebaum BC Rabe T Kiesel L 6 December 2012 Female Contraception Update and Trends Springer Science amp Business Media pp 429 ISBN 978 3 642 73790 9 Artini PG Genazzani AR Petraglia F 11 December 2001 Advances in Gynecological Endocrinology CRC Press pp 105 ISBN 978 1 84214 071 0 King TL Brucker MC Kriebs JM Fahey JO 21 October 2013 Varney s Midwifery Jones amp Bartlett Publishers pp 495 ISBN 978 1 284 02542 2 a b Jurow R Shoupe D 7 November 2007 Long Acting Progestin Injectables Comparison ofDepo Provera With Depo SubQProvera 104 In Shoupe D Kjos SL eds The Handbook of Contraception A Guide for Practical Management Springer Science amp Business Media pp 103 ISBN 978 1 59745 150 5 Plattner PA Heusser H Herzig PT 1949 Uber steroide und sexualhormone 159 Die synthese von 17 methyl progesteron Helvetica Chimica Acta 32 1 270 275 doi 10 1002 hlca 19490320138 PMID 18115956 ACRH U S Dept of Energy 1960 p 71 The minimal activity of 17 a hydroxyprogesterone is magnified to an unexpected degree by the esterification of this steroid with caproic acid to produce 17 a hydroxyprogesterone 17 n caproate first reported by Karl Junkmann in 1954 6 7 Dorfman RI 1966 Methods in Hormone Research Academic Press p 86 Junkmann 1954 reported that the acetate butyrate and caproate forms had both increased and prolonged activity Kirk RE Othmer DF Mark HF 1965 Encyclopedia of chemical technology Interscience Publishers p 78 Subsequent acetylation with acetic anhydride and tosyl acid followed by Oppenauer oxidation afforded 17a acetoxy progesterone 95 in good yield 115 Tests showed this compound to possess 2 3 times the oral activity of 17 methylpregn 4 ene 3 20 dione 78 and to be many times more potent than progesterone 116 117 Pure bred Dogs American Kennel Gazette American Kennel Club 1961 p 33 According to Dr Gordon G Stocking director of Upjohn s Veterinary Division Prodox is a synthetic version of progesterone one of the hormones that regulates the human female reproductive system It is 100 per cent effective and has produced no ill effects on 200 or more dogs on which it has been tested As a result of its findings says Dr Stocking Upjohn is making the product available through veterinarians a b Hydroxyprogesterone injection Uses Side Effects amp Warnings Index Nominum 2000 International Drug Directory Taylor amp Francis 2000 pp 532 ISBN 978 3 88763 075 1 Sweetman SC ed 2009 Sex hormones and their modulators Martindale The Complete Drug Reference 36th ed London Pharmaceutical Press p 2110 ISBN 978 0 85369 840 1 Retrieved from https en wikipedia org w index php title Hydroxyprogesterone acetate amp oldid 1169036386, wikipedia, wiki, book, books, library,

article

, read, download, free, free download, mp3, video, mp4, 3gp, jpg, jpeg, gif, png, picture, music, song, movie, book, game, games.