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| Clinical data | |
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| Trade names | Ginotex, Lovelle, Minique, Ondeva, Totelle, others |
| Other names | TMG; RU-27987; 21(S)-Hydroxypromegestone; 21β-Hydroxypromegestone; 21(S)-Hydroxy-17α,21-dimethyl-9-dehydro-19-norprogesterone; 21(S)-Hydroxy-17α,21-dimethyl-19-norpregna-4,9-dien-3,20-dione; 17β-(S)-Lactoyl-17α-methylestra-4,9-dien-3-one; 17β-((S)-2-Hydroxypropanoyl)-17α-methylestra-4,9-dien-3-one |
| Routes of administration | By mouth |
| Drug class | Progestogen;Progestin |
| ATC code | |
| Legal status | |
| Legal status |
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| Pharmacokinetic data | |
| Bioavailability | 100%[1] |
| Protein binding | 98% (toalbumin)[2] |
| Metabolism | Mainlyhydroxylation[2] |
| Eliminationhalf-life | Range: 12–20 hours[3] Mean: 13.8–15.6 hours[2][4] |
| Identifiers | |
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| CAS Number | |
| PubChemCID | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEBI | |
| ChEMBL | |
| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.189.099 |
| Chemical and physical data | |
| Formula | C22H30O3 |
| Molar mass | 342.479 g·mol−1 |
| 3D model (JSmol) | |
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Trimegestone, sold under the brand namesOndeva andTotelle among others, is aprogestin medication which is used inmenopausal hormone therapy and in the prevention ofpostmenopausalosteoporosis.[4][2][3] It was also under development for use inbirth control pills to preventpregnancy, but ultimately was not marketed for this purpose.[5] The medication is available alone or in combination with anestrogen.[6][7] It is takenby mouth.[2]
Side effects of trimegestone includeheadache,breast tenderness,nervousness,abdominal pain,bloating,muscle cramps,nausea,depression, andvaginal bleeding among others.[8][4] Trimegestone is a progestin, or asyntheticprogestogen, and hence is anagonist of theprogesterone receptor, thebiological target of progestogens likeprogesterone.[2][4] It has weakantiandrogenic andantimineralocorticoid activity and no other importanthormonal activity.[2][4]
Trimegestone was first described in 1979 and was introduced for medical use in 2001.[9][10][11] It is sometimes described as a "fourth-generation" progestin.[12][13] The medication is marketed throughoutEurope andLatin America.[14][6] It is not available in theUnited States orCanada.[15][14][6]
Trimegestone is used inmenopausal hormone therapy in the treatment ofmenopausalsymptoms such ashot flashes andvaginal atrophy and in the prevention ofpostmenopausalosteoporosis.[16][10][3][7]
Trimegestone is available both alone (as Ondeva) and in combination withestradiol (as Ginotex, Lovelle, Minique, Totelle), both of which are approved for the treatment of menopausal symptoms and prevention of postmenopausal osteoporosis.[7][17] Preparations of trimegestone are oral tablets and contain 0.1 to 0.5 mg of the medication.[18]
The most commonside effects of trimegestone alone at dosages of 0.25 to 0.5 mg/day includebreast tenderness (40.7–43.0%),abdominal pain (13.9–16.7%),headache (16.0–19.4%),nervousness (12.7–16.0%),bloating (10.3–16.0%),muscle cramps (12.3–13.9%),nausea (4.8–12.3%), anddepression (3.0–3.1%).[8] The most commonside effects of the combination of 1 mg/dayestradiol and 0.125–0.25 mg/day trimegestone include headache (26.4%), breast pain (15–20%), abdominal pain (18%), andvaginal bleeding (9–18%), andmetrorrhagia (18.8%).[4]
Trimegestone is aprogestogen, or anagonist of theprogesterone receptor (PR).[19][2][20] It has very highaffinity for the PR, about 588 to 660% of that ofprogesterone.[19][2][20] This is greater than that of almost all other widely used progestins, with the exception of the19-nortestosteronederivativegestodene (which has about 864% of the affinity of progesterone).[19][21][2][20] In accordance with its very high affinity for the PR, trimegestone is described as a verypotent progestogen, showing secretory transformation of the estrogen-treatedendometrium at a dosage of only 0.1 mg/day, and is the most potent progestin of the19-norprogesterone group.[16][2] Like other progestogens, trimegestone has functionalantiestrogenic effects in certaintissues such as theendometrium and hasantigonadotropic effects.[2][22] Theendometrial transformation dosage of trimegestone is 0.25 to 0.5 mg/day and itsovulation-inhibiting dosage is 0.5 mg/day.[21][2]
In addition to its affinity for the PR, trimegestone has moderate affinity for themineralocorticoid receptor (42–120% of that ofaldosterone), weak to very weak affinity for theglucocorticoid andandrogen receptors (9–13% of that ofdexamethasone and 1–2.4% of that oftestosterone, respectively), and no affinity for theestrogen receptor (less than 0.02% of that ofestradiol).[19][2][20] In accordance, it possesses weakantimineralocorticoid activity, very weakantiandrogenic activity, and noandrogenic,estrogenic,glucocorticoid,antiglucocorticoid, ormineralocorticoid activity.[2][19][4][20] As such, it is aselective and mostly pure progestogen.[16][2] Unlikeprogesterone, trimegestone does notmetabolize intoneurosteroids and hence does not influenceGABAA receptor signaling or producesedativeside effects.[19]
The antiandrogenic potency of trimegestone in animals is about 30% of that ofcyproterone acetate.[23]
Theoralbioavailability of trimegestone is about 100%.[1][3] Following a single oral dose of trimegestone,peak serum concentrations occur within 0.5 hours and are 12–15 ng/mL (35–44 nmol/L) for a 0.5 mg dose and 25 ng/mL (73 nmol/L) for a 1 mg dose.[2][3] Circulating levels of trimegestone increase proportionally across dosages of 0.25 to 1 mg/day.[3]Steady-state levels of trimegestone are achieved within 3 days of daily administration.[3] Theplasma protein binding of trimegestone is 98%; it is bound toalbumin.[2] Trimegestone ismetabolized mainly viahydroxylation.[2][22] The 1β- and 6β-hydroxymetabolites of trimegestone are progestogens with considerable potency similarly and show little or noaffinity to othersteroid hormone receptors.[22] Theelimination half-life of trimegestone is between 12 and 20 hours, with an average of about 13.8 to 15.6 hours.[2][3][4]
Trimegestone, also known as 21(S)-hydroxy-17α,21-dimethyl-δ9-19-norprogesterone or as 21(S)-hydroxy-17α,21-dimethyl-19-norpregna-4,9-dien-3,20-dione, is asyntheticnorpregnanesteroid and aderivative ofprogesterone.[24][2] It is specifically a combined derivative of17α-methylprogesterone and19-norprogesterone, or of17α-methyl-19-norprogesterone.[24][2] Related derivatives of 17α-methyl-19-norprogesterone includedemegestone andpromegestone.[24][2]
Trimegestone was first described in 1979 and was introduced for medical use in 2001.[9][10][11] It was discovered as anactive metabolite ofpromegestone.[9][21][25] The medication originated bySanofi-Aventis inFrance, where promegestone was developed, and was first marketed byWyeth inSweden.[26]
Trimegestone is thegeneric name of the drug and itsINNTooltip International Nonproprietary Name,USANTooltip United States Adopted Name, andBANTooltip British Approved Name, whiletrimégestone is itsDCFTooltip Dénomination Commune Française.[24][6][27] It is also known by its developmental code nameRU-27987.[24][6][27]
Trimegestone under the brand names Ginotex, Lovelle, Lovelle Ciclico, Lovelle Continuo, Minique, Ondeva, Totelle, Totelle Ciclico, Totelle Ciclo, Totelle Continuo, Totelle Cycle, Totelle Cyclo, Totelle Secuencial, and Totelle Sekvens.[14][6][27][11][3][28] With the exception of Ondeva, which is formulated alone, all of these products are formulated in combination withestradiol.[14][6][27]
Trimegestone is or has been marketed inEurope andLatin America, including inArgentina,Austria,Belgium,Brazil,Chile,Denmark,Finland,France,Italy,Lithuania,Mexico,Norway,Sweden, andVenezuela.[14][6][26][3][27] It is not available in any predominantlyEnglish-speaking countries, including theUnited States,Canada, theUnited Kingdom,Ireland,Australia,New Zealand, orSouth Africa.[15][14][6]
The oral combination of trimegestone andethinylestradiol was under development byWyeth in theUnited States as abirth control pill to preventpregnancy and the oral combination of trimegestone andconjugated estrogens was under development by Wyeth in the United States to treatmenopausal syndrome and to preventpostmenopausalosteoporosis, but the development of both formulations was discontinued and they were never marketed.[5][29] Atransdermal patch with the developmental code namePSK-3987 containingestradiol and trimegestone was under development by ProStrakan for the treatment of menopausal syndrome, but it too never completed development and hence was not marketed.[30]
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