Promegestone was first described in 1973 and was introduced for medical use inFrance in 1983.[9][10][11] It has only been marketed in a few countries, including France,Portugal,Tunisia, andArgentina.[6][12] In addition to its use as a medication, promegestone has been widely used inscientific research as aradioligand of the progesterone receptor.[4][13]
Followingoral administration,peak serum levels of promegestone are reached after 1 to 2 hours.[1][3] The medication is mainlybound toalbumin; it does not bind tosex hormone-binding globulin, and binds only weakly tocorticosteroid-binding globulin.[1][3][17] Themetabolism of promegestone is mainly viahydroxylation at the C21 position and at other positions.[1][3] Progesterone is similarly hydroxylated at the C21 position, into11-deoxycorticosterone (21-hydroxyprogesterone).[18] However, the C9(10)double bond of promegestone greatly limits the A-ringreduction that progesterone undergoes, resulting in 21-hydroxylation being the main route of metabolism for promegestone.[18] The medication isstereoselectively metabolized intotrimegestone, the 21(S)-hydroxymetabolite, which is the main compound found inplasma; 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 aprodrug 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] Theelimination half-life of trimegestone is 13.8 to 15.6 hours.[1][2] Promegestone, trimegestone, and 21(R)-hydroxypromegestone are notexcreted inurine, while 3% of a dose is recovered as theglucuronide and/orsulfateconjugate 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 inFrance in 1983.[9][10][11][5] It was developed byRoussel Uclaf in France.[5]
Promegestone is thegeneric name of the drug and itsINNTooltip International Nonproprietary Name, whilepromégestone is itsDCFTooltip Dénomination Commune Française.[6][9][12] It is also known by its developmental code nameR-5020 orRU-5020.[6][9][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.
