Nestorone

370.48200

370.48

9AMX4Q13CC

60.44000

4.18520

1.15g/cm3

178-179°

499.3ºC at 760mmHg

216.2ºC

1.549

Insoluble

NONH for all modes of transport

3

|Warning|H351 (100%): Suspected of causing cancer [Warning Carcinogenicity]|P201, P202, P281, P308+P313, P405, and P501|Aggregated GHS information provided by 2 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

There have been no reports of serious ill effects from overdose of combination hormonal contraceptive use. Overdosage may cause withdrawal bleeding in females and nausea. In case of suspected overdose, all vaginal systems containing segesterone acetate should be removed and symptomatic treatment should be initiated. In a 2-year carcinogenicity study in rats receiving segesterone acetate via subdermal implants, there was no drug-related increase in tumor incidence. In a 2-year intravaginal carcinogenicity study in mice, segesterone acetate gel produced an increased incidence of adenocarcinoma and lobular hyperplasia in the breast at a supratherapeutic dose of 30 mg/kg/day. Segesterone acetate was not shown to be mutagenic or clastogenic.

Serum protein binding of segesterone acetate is approximately 95% and it displays negligible binding affinity for sex hormone-binding globulin (SHBG).

Segesterone acetate in combination with ethinyl estradiol is indicated for use by females of reproductive potential to prevent pregnancy as a combination hormonal contraceptive (CHC). It induces contraception for thirteen 28-day cycles (1 year) following vaginal administration. The vaginal system must remain in place continuously for 3 weeks (21 days) followed by a 1-week (7-day) vaginal system-free interval. The use in females with a body mass index of >29 kg/m^2 has not been adequately evaluated.|FDA Label

Segesterone acetate suppresses ovulation. In a Phase I randomized, placebo-controlled, randomized crossover study involving healthy adult female subjects, there was no clinically significant QTc interval prolongation following a single intravenous bolus dose of segesterone acetate. Segesterone acetate shows no androgenic, anabolic, or estrogenic activity. It also did not show uterotropic activity in ovariectomized rats. In the endometrial transformation test to assess the progestational activity, dose-dependent increases in both uterine weight was observed following subcutaneous administration of segesterone acetate.

Chemical substances or agents with contraceptive activity in females. Use for female contraceptive agents in general or for which there is no specific heading. (See all compounds classified as Contraceptive Agents, Female.)|Contraceptive agents that act on the ENDOCRINE SYSTEM. (See all compounds classified as Contraceptive Agents, Hormonal.)

Contraceptive vaginal rings provided sustained release of contraceptive levels of segesterone acetate over 90 days in a pharmacokinetic study of healthy women. Following vaginal administration for up to 13 cycles, segesterone acetate was absorbed into systemic administration and reached the peak plasma concentration in 2 hours in Cycle 1, Cycle 3, and Cycle 13. Concentrations declined after time to reach plasma concentration (Tmax) and became more constant after 96 hours post-dose.Over subsequent cycles of use, the peak serum concentrations of segesterone acetate decreased. In Cycle 1, 3 and 13, the peak plasma concentrations were 1147, 363, and 294 pg/mL.|In a pharmacokinetic study, approximately 81.4% and 7.62% of the subcutaneously-administered dose in rats was excreted via feces and urine, respectively.|The volume of distribution of segesterone acetate is 19.6 L/kg.|No pharmacokinetic data available.

Segesterone acetate undergoes rapid metabolism and inactivation in the liver. Based on the findings _in vitro_, the major oxidative metabolites in the serum include 5α-dihydro- and 17α-hydroxy-5α­-dihydro metabolites constitute about 50% of exposure relative to segesterone acetate. The metabolites are not pharmacologically active with EC50 to progesterone receptor 10-fold higher than that of the parent compound. It was shown that 3α, 5α-tetrahydrosegesterone acetate acts as an activator at the GABA-A receptors in the brain.

The mean (SD) half life of segesterone acetate is 4.5 (3.4) hours.

Segesterone acetate selectively binds to the progesterone receptor (PR), a transcription factor belonging to the nuclear receptor superfamily, where it acts as an agonist and transactivator. According to the findings from docking experiments, it adopts the same docking position within the PR ligand-binding domain (LBD) as progesterone but due to additional stabilizing contacts between 17α-acetoxy and 16-methylene groups and PR LBD, segesterone acetate display higher potency than progesterone. As with other progestins, segesterone acetate prevents ovulation by blocking the midcycle surge in luteinizing hormone (LH) secretion, thereby inhibiting the development of ovarian follicles. When used in combination with segesterone acetate, ethinyl estradiol potentiates the antigonadotropic of the progestin and prevents irregular shedding of the endometrium. Segesterone acetate lacks androgenic activity, and displayed binding affinity to androgen receptors that was 500- to 600-fold less than that of testosterone. It does not display binding affinity toward estrogen receptors. When the relative binding affinities of segesterone acetate to human steroid receptors were investigated _in vitro_, it was demonstrated that segesterone acetate binds to the glucocorticoid receptor. However, segesterone acetate did not exert any glucocorticoid activity in the _in vivo_ assays showing no increase in liver glycogen and tyrosine transaminase TAT.

16-methylene-17alpha-acetoxy-19-nor-4-pregnen-3,20-dione

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients