Promegestone

Promegestone
Clinical data
Trade names	Surgestone
Other names	PMG; R-5020; RU-5020; 17α,21-Dimethyl-δ9-19-norprogesterone; 17α,21-Dimethyl-19-norpregna-4,9-diene-3,20-dione
Routes of; administration	By mouth
Drug class	Progestogen; Progestin
ATC code	G03DB07 (WHO) ;
Pharmacokinetic data
Protein binding	To albumin
Metabolism	Liver (hydroxylation)
Metabolites	• Trimegestone
Elimination half-life	Promegestone: ?; Trimegestone: 13.8–15.6 hours
Identifiers
	IUPAC name (8S,13S,14S,17S)-13,17-dimethyl-17-propionyl-1,2,6,7,8,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one;
CAS Number	34184-77-5;
PubChem CID	36709;
ChemSpider	33716;
UNII	9XE0V2SQYX;
KEGG	D08431;
ChEBI	CHEBI:73390;
ChEMBL	ChEMBL196003;
CompTox Dashboard (EPA)	DTXSID4036510 ;
ECHA InfoCard	100.207.681
Chemical and physical data
Formula	C22H30O2
Molar mass	326.480 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CCC(=O)[C@]1(CC[C@@H]2[C@@]1(CCC3=C4CCC(=O)C=C4CC[C@@H]23)C)C;
	InChI InChI=1S/C22H30O2/c1-4-20(24)22(3)12-10-19-18-7-5-14-13-15(23)6-8-16(14)17(18)9-11-21(19,22)2/h13,18-19H,4-12H2,1-3H3/t18-,19+,21+,22-/m1/s1; Key:QFFCYTLOTYIJMR-XMGTWHOFSA-N;

Promegestone, sold under the brand name Surgestone, is a progestin medication which is used in menopausal hormone therapy and in the treatment of gynecological disorders.^[4]^[1]^[5]^[6] It is taken by mouth.^[1]

Side effects of promegestone include menstrual irregularities among others.^[7] Promegestone is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone.^[1] It has weak antiandrogenic, glucocorticoid, and antimineralocorticoid activity and no other important hormonal activity.^[1]^[8]^[2] The medication is largely a prodrug of trimegestone.^[7]^[1]

Promegestone was first described in 1973 and was introduced for medical use in France in 1983.^[9]^[10]^[11] It has only been marketed in a few countries, including France, Portugal, Tunisia, and Argentina.^[6]^[12] In addition to its use as a medication, promegestone has been widely used in scientific research as a radioligand of the progesterone receptor.^[4]^[13]

^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ Cite error: The named reference pmid16112947 was invoked but never defined (see the help page).
^ ^a ^b Cite error: The named reference pmid17616854 was invoked but never defined (see the help page).
^ Cite error: The named reference Kuhl2011 was invoked but never defined (see the help page).
^ ^a ^b Raynaud JP, Ojasoo T (1983). "[Promegestone, a new progestin]". Journal de Gynécologie, Obstétrique et Biologie de la Reproduction (in French). 12 (7): 697–710. PMID 6366037.
^ Allen RC (11 September 1984). "To Market – 1983". In Baily DM (ed.). Annual Reports in Medicinal Chemistry. Vol. 19. Academic Press. pp. 323–. ISBN 978-0-08-058363-1.
^ ^a ^b "List of Progestins".
^ ^a ^b Tulunay FC, Orme M (6 December 2012). European Collaboration: Towards Drug Developement [sic] and Rational Drug Therapy: Proceedings of the Sixth Congress of the European Association for Clinical Pharmacology and Therapeutics Istanbul, June 24–28, 2003. Springer Science & Business Media. pp. 107–. ISBN 978-3-642-55454-4. Investigation of the Pharmacokinetics and Metabolism of Promegestone in Healthy Female Volunteers Following Single Oral Administration of 1 mg Promegestone I Gualano V., 1Geneteau A., I Chassard D., I Fordham P., 2Schatz B. I Aster-Cephac, 3/5, Rue Eugene Millon, 75015 Paris, France 2Laboratoire Aventis, 46 Quai De La Rapee, F-75601 Paris Cedex 12, France. A single 1 mg oral dose of promegestone (Surgestonee, 2x0.5 mg) was given to 12 healthy premenopausal women. The aims were to determine the concentrations of promegestone and its metabolites and their pharmacokinet-ic parameters. Blood and urine samples were followed until 96 hours post dose. To avoid any interference with natural hormones, promegestone was given between day 7 and 10 of the menstrual cycle. Clinical safety and tolerability were good. Most of the minor adverse events observed were estimated possibly linked to the study drug (menstrual disorders) because classically related to progestins therapy. In addition, no clinically relevant biological modifications were observed. There was a stereoselective metabolism of promegestone in favor of the 21S hydroxy-promegestone, the main circulating compound in plasma (AUC ratio 5/R of about 21). Levels of 21S hydroxy-promegestone are about twice greater than that of unchanged promegestone. The plasma levels of the second metabolite, i.e. 21 R hydroxy-promegestone are far below these of either promegestone and 21S hydroxy-promegestone. Promegestone, 215 hydroxy- and 21R hydroxy-promegestone are not excreted in urine. About 3% of the dose was recov-ered in urine as sulfo and/or glucuro-conjugate 21S hydroxy-promegestone and about 1% of the dose as sulfo and/or glucuro conjugate 21R hydroxy-promegestone.
^ Cite error: The named reference pmid14667983 was invoked but never defined (see the help page).
^ Cite error: The named reference Elks2014 was invoked but never defined (see the help page).
^ Cite error: The named reference pmid4353432 was invoked but never defined (see the help page).
^ Cite error: The named reference Publishing2013 was invoked but never defined (see the help page).
^ Cite error: The named reference IndexNominum2000 was invoked but never defined (see the help page).
^ Raynaud JP, Ojasoo T, Vaché V (1981). "Stable and Specific Tracers". Reproductive Processes and Contraception. Biochemical Endocrinology. Springer. pp. 163–179. doi:10.1007/978-1-4684-3824-6_7. ISBN 978-1-4684-3826-0.

[pmid16112947-1] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ Cite error: The named reference pmid16112947 was invoked but never defined (see the help page).

[pmid17616854-2] Cite error: The named reference pmid17616854 was invoked but never defined (see the help page).

[Kuhl2011-3] Cite error: The named reference Kuhl2011 was invoked but never defined (see the help page).

[pmid6366037-4] Raynaud JP, Ojasoo T (1983). "[Promegestone, a new progestin]". Journal de Gynécologie, Obstétrique et Biologie de la Reproduction (in French). 12 (7): 697–710. PMID 6366037.

[Cain1984-5] Allen RC (11 September 1984). "To Market – 1983". In Baily DM (ed.). Annual Reports in Medicinal Chemistry. Vol. 19. Academic Press. pp. 323–. ISBN 978-0-08-058363-1.

[Drugs.com-6] "List of Progestins".

[TulunayOrme2012-7] Tulunay FC, Orme M (6 December 2012). European Collaboration: Towards Drug Developement [sic] and Rational Drug Therapy: Proceedings of the Sixth Congress of the European Association for Clinical Pharmacology and Therapeutics Istanbul, June 24–28, 2003. Springer Science & Business Media. pp. 107–. ISBN 978-3-642-55454-4. Investigation of the Pharmacokinetics and Metabolism of Promegestone in Healthy Female Volunteers Following Single Oral Administration of 1 mg Promegestone I Gualano V., 1Geneteau A., I Chassard D., I Fordham P., 2Schatz B. I Aster-Cephac, 3/5, Rue Eugene Millon, 75015 Paris, France 2Laboratoire Aventis, 46 Quai De La Rapee, F-75601 Paris Cedex 12, France. A single 1 mg oral dose of promegestone (Surgestonee, 2x0.5 mg) was given to 12 healthy premenopausal women. The aims were to determine the concentrations of promegestone and its metabolites and their pharmacokinet-ic parameters. Blood and urine samples were followed until 96 hours post dose. To avoid any interference with natural hormones, promegestone was given between day 7 and 10 of the menstrual cycle. Clinical safety and tolerability were good. Most of the minor adverse events observed were estimated possibly linked to the study drug (menstrual disorders) because classically related to progestins therapy. In addition, no clinically relevant biological modifications were observed. There was a stereoselective metabolism of promegestone in favor of the 21S hydroxy-promegestone, the main circulating compound in plasma (AUC ratio 5/R of about 21). Levels of 21S hydroxy-promegestone are about twice greater than that of unchanged promegestone. The plasma levels of the second metabolite, i.e. 21 R hydroxy-promegestone are far below these of either promegestone and 21S hydroxy-promegestone. Promegestone, 215 hydroxy- and 21R hydroxy-promegestone are not excreted in urine. About 3% of the dose was recov-ered in urine as sulfo and/or glucuro-conjugate 21S hydroxy-promegestone and about 1% of the dose as sulfo and/or glucuro conjugate 21R hydroxy-promegestone.

[pmid14667983-8] Cite error: The named reference pmid14667983 was invoked but never defined (see the help page).

[Elks2014-9] Cite error: The named reference Elks2014 was invoked but never defined (see the help page).

[pmid4353432-10] Cite error: The named reference pmid4353432 was invoked but never defined (see the help page).

[Publishing2013-11] Cite error: The named reference Publishing2013 was invoked but never defined (see the help page).

[IndexNominum2000-12] Cite error: The named reference IndexNominum2000 was invoked but never defined (see the help page).

[RaynaudOjasoo1981-13] Raynaud JP, Ojasoo T, Vaché V (1981). "Stable and Specific Tracers". Reproductive Processes and Contraception. Biochemical Endocrinology. Springer. pp. 163–179. doi:10.1007/978-1-4684-3824-6_7. ISBN 978-1-4684-3826-0.

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Promegestone

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