Ethinyl estradiol, Etonogestrel

Pharmacological properties

mechanism of action. Novaring ring contains etonogestrel and ethinyl estradiol. etonogestrel is a progestogen, a derivative of 19-nortestosterone, which has a high affinity for progesterone receptors in target organs. ethinyl estradiol is an estrogen widely used in contraceptive preparations. the contraceptive effect of novaring is based on various mechanisms, the main of which is the inhibition of ovulation.

Efficiency and safety. Clinical studies were conducted in different countries of the world (USA, European Union countries and Brazil) among women aged 18-40 years. The detected contraceptive effect was at least at the level of that for combined oral contraceptives (CPC).

Table 1. The number of pregnancies per 100 women-years of use (Pearl index) according to the results of clinical studies of the drug NovaRing

Analysis method	Pearl Index	95% confidence interval	The number of cycles
ITT (users + cases of method inefficiency)	0,96	0,64–1,39	37 977
PP (method inefficiency)	0,64	0,35–1,07	28 723

When taking higher doses of CPC (0.05 mg ethinyl estradiol), the risk of developing endometrial and ovarian cancer is reduced. It remains to be determined whether these benefits can be attributed to such low-dose hormonal contraceptives as NovaRing.

The nature of the bleeding. According to a clinical study of the effect of the NovaRing drug (n = 512) on the nature of menstrual bleeding for 13 cycles, the incidence of breakthrough spotting or bleeding in the NovaRing group (2.0-6.4%) was significantly lower than against the background application of CPC 150/30 μg levonorgestrel / ethinyl estradiol (n = 518). In most women (58.8–72.8%), vaginal bleeding was limited to the period when NovaRing was not used.

Effect on bone mineral density. A 2-year study of the effect of NovaRing (n = 76) on bone mineral density compared with that of a non-hormonal intrauterine contraceptive (n = 31) revealed no undesirable effects.

Children. The safety and effectiveness of NovaRing for teenage girls (under the age of 18 years) have not been studied.

Pharmacokinetics Etonogestrel

Absorption. Etonogestrel released from the NovaRing ring is rapidly absorbed in the vaginal mucosa. WITH_max etonogestrel in blood plasma (an average of 1700 pg / ml) is achieved for approximately 1 week after the introduction of the ring. This plasma concentration changes slightly and slowly decreases to 1600 pg / ml after 1 week, 1500 pg / ml after 2 weeks and 1400 pg / ml after 3 weeks. Absolute bioavailability is 100% (which is higher than when using oral contraceptives). The levels of etonogestrel in the cervix and uterine cavity when using the NovaRing drug were similar to the levels of etonogestrel with the use of an oral contraceptive containing 0.150 mg of desogestrel and 0.020 mg of ethinyl estradiol.

Distribution. Etonogestrel combines with albumin and plasma globulin that bind sex hormones. The volume of distribution of etonogestrel is 2.3 l / kg body weight.

Metabolism. Etonogestrel is metabolized by known steroid metabolism pathways. The rate of excretion of metabolites from blood plasma averages 3.5 l / h. Interactions of etonogestrel with ethylene estradiol taken simultaneously were not detected.

The concentration of etonogestrel in blood plasma is reduced in 2 stages. T_½ at the last stage, it is about 29 hours. Etonogestrel and its metabolites are excreted in the urine and bile in a ratio of 1.7: 1. T_½ metabolites is about 6 days.

Ethinyl estradiol

Absorption. Ethinyl estradiol released from the NovaRing ring is rapidly absorbed in the vaginal mucosa. WITH_max in blood plasma (about 35 pg / ml) is achieved approximately on the 3rd day after the introduction of the ring and decreases to 19 pg / ml after 1 week, 18 pg / ml after 2 weeks and 18 pg / ml after 3 weeks.Monthly Systemic Ethinyl Estradiol (AUC)_0–∞) from the drug NovaRing is 10.9 ng / ml. The absolute bioavailability is 56%, which corresponds to the level of bioavailability of ethinyl estradiol when taken orally. Ethinyl estradiol levels in the cervix and int