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]
Following
oral administration,
peak serum levels of promegestone are reached after 1 to 2 hours.[1][3] The medication is mainly
bound to
albumin; it does not bind to
sex hormone-binding globulin, and binds only weakly to
corticosteroid-binding globulin.[1][3][17] The
metabolism of promegestone is mainly via
hydroxylation at the C21 position and at other positions.[1][3] Progesterone is similarly hydroxylated at the C21 position, into
11-deoxycorticosterone (21-hydroxyprogesterone).[18] However, the C9(10)
double bond of promegestone greatly limits the A-ring
reduction that progesterone undergoes, resulting in 21-hydroxylation being the main route of metabolism for promegestone.[18] The medication is
stereoselectively metabolized into
trimegestone, the 21(S)-hydroxy
metabolite, which is the main compound found in
plasma; it circulates at levels approximately twice those of promegestone itself.[7] In addition, trimegestone has more than three-fold higher affinity for the PR than does promegestone.[1] As such, promegestone is largely a
prodrug of trimegestone.[7][19] A second metabolite, 21(R)-hydroxypromegestone, circulates at far lower concentrations (
AUCTooltip area-under-the-curve levels ratio for the (S)- and (R)-
isomers of about 21).[7] The
elimination half-life of trimegestone is 13.8 to 15.6 hours.[1][2] Promegestone, trimegestone, and 21(R)-hydroxypromegestone are not
excreted in
urine, while 3% of a dose is recovered as the
glucuronide and/or
sulfateconjugate of trimegestone and 1% of a dose is recovered as the glucuronide and/or sulfate conjugate of 21(R)-hydroxypromegestone.[7]
Promegestone was first described in the literature in 1973 and was introduced for medical use in
France in 1983.[9][10][11][5] It was developed by
Roussel Uclaf in France.[5]
Society and culture
Generic names
Promegestone is the
generic name of the drug and its
INNTooltip International Nonproprietary Name, while promégestone is its
DCFTooltip Dénomination Commune Française.[6][9][12] It is also known by its developmental code name R-5020 or RU-5020.[6][9][12]
Brand names
Promegestone is marketed exclusively under the brand name Surgestone.[6][12]
^
abcdSitruk-Ware R, Bossemeyer R, Bouchard P (June 2007). "Preclinical and clinical properties of trimegestone: a potent and selective progestin". Gynecological Endocrinology. 23 (6): 310–319.
doi:
10.1080/09513590701267727.
PMID17616854.
S2CID39422122.
^
abcdefghiKuhl H (2011).
"Pharmacology of progestogens"(PDF). Journal für Reproduktionsmedizin und Endokrinologie-Journal of Reproductive Medicine and Endocrinology. 8 (Special Issue 1): 157–176.
^
abcRaynaud JP, Ojasoo T (1983). "[Promegestone, a new progestin]". Journal de Gynécologie, Obstétrique et Biologie de la Reproduction (in French). 12 (7): 697–710.
PMID6366037.
^
abcdefgTulunay 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–.
ISBN978-3-642-55454-4. 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.
^
abRaynaud 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.
ISBN978-1-4684-3826-0.
^Gourdy P, Bachelot A, Catteau-Jonard S, Chabbert-Buffet N, Christin-Maître S, Conard J, et al. (November 2012). "Hormonal contraception in women at risk of vascular and metabolic disorders: guidelines of the French Society of Endocrinology". Annales d'Endocrinologie. 73 (5): 469–487.
doi:
10.1016/j.ando.2012.09.001.
PMID23078975.
^Blanton MP, Xie Y, Dangott LJ, Cohen JB (February 1999). "The steroid promegestone is a noncompetitive antagonist of the Torpedo nicotinic acetylcholine receptor that interacts with the lipid-protein interface". Molecular Pharmacology. 55 (2): 269–278.
doi:
10.1124/mol.55.2.269.
PMID9927618.
S2CID491327.
^Chan DW, Slaunwhite WR (May 1977). "The binding of a synthetic progestin, R5020 to transcortin and serum albumin". The Journal of Clinical Endocrinology and Metabolism. 44 (5): 983–985.
doi:
10.1210/jcem-44-5-983.
PMID858781.
Raynaud JP, Ojasoo T (1983). "[Promegestone, a new progestin]". Journal de Gynécologie, Obstétrique et Biologie de la Reproduction (in French). 12 (7): 697–710.
PMID6366037.
Brun G, Dargent D, Pontonnier G, Petrescou L (May 1984). "[Clinical use of promegestone, a progestational agent with high specificity for receptors]". Revue Française de Gynécologie et d'Obstétrique (in French). 79 (5): 423–426.
PMID6396815.