Synfonia Mechanism of Action

Pharmacology: Pharmacodynamics: The contraceptive effect of combined oral contraceptives is based on the interaction of various factors, the most important of which are seen as the inhibition of ovulation and the changes in the cervical secretion and endometrium.
Drospirenone has beneficial properties in addition to contraception. Drospirenone has antimineralocorticoid activity that can prevent weight gain and other symptoms caused by fluid retention. It counteracts the estrogen-related sodium retention, providing for a very good tolerance and has positive effects on the premenstrual syndrome (PMS). Drospirenone 3 mg and ethinylestradiol 0.02 mg 24+4 tablets, a shortened hormone free interval, was studied in premenstrual dysphoric disorder (PMDD). PMDD is a severe form of PMS. It showed clinical superiority in relief of symptoms of PMDD in comparison with placebo.
In combination with ethinylestradiol, drospirenone displays a favorable lipid profile with an increase in HDL. Drospirenone exerts antiandrogenic activity leading to a positive effect on the skin and toa reduction in acne lesions and sebum production, reduction in greasiness of the skin and hair.
In addition, drospirenone does not counteract the ethinylestradiol-related sex hormone binding globulin (SHBG) increase which is useful for binding and inactivation of the endrogenous androgens. Drospirenone has no androgenic, estrogenic, glucocorticoid and antiglucocorticoid activity. This gives drospirenone a pharmacological profile closely resembling the natural hormone progesterone.
Pharmacokinetics: Drospirenone: Absorption: Orally administered drospirenone is rapidly and almost completely absorbed. Bioavailability is between 76 and 85%. Concomitant ingestion of food has no influence on the bioavailability of drospirenone.
Distribution: After oral administration, serum drospirenone levels decrease with a terminal half-life approximately 30 hours. Drospirenone is bound to serum albumin and does not bind to sex hormone binding globulin (SHBG) or corticoid binding globulin (CBG).
Metabolism: Drospirenone is extensively metabolized after oral administration. The major metabolites in the plasma are the acid form of drospirenone which are formed without involvement of the P450 system. Drospirenone is metabolized to a minor extent by cytochrome P450 3A4.
Elimination: Drospirenone is excreted only in trace amounts in unchanged form. The metabolites of drospirenone are excreted with the faeces and urine, the half-life of metabolite excretion with the urine and feces is about 40 hours.
Ethinylestradiol: Absorption: Orally administered ethinylestradiol is absorbed rapidly and completely. Absolute bioavailability as a result of presystemic conjugation and first-pass metabolism is approximately 60%.
Distribution: Serum ethinylestradiol levels decrease in two phases, the terminal disposition phase is characterized by a half-life of approximately 24 hours. Ethinylestradiol is highly but non-specifically bound to serum albumin (approximately 98.5%), and induces an increase in the serum concentrations of sex hormone binding globulin (SHBG) and corticoid binding globulin (CBG).
Metabolism: Ethinylestradiol is subject to presystemic conjugation in both small bowel mucosa and the liver. Ethinylestradiol is primarily metabolized as free metabolites and as conjugates with glucuronides and sulfate.
Elimination: Ethinylestradiol is not excreted in unchanged form to any significant extent. The metabolites of ethinylestradiol are excreted at a urinary to biliary ratio of 4:6. The half-life of metabolite excretion is about 1 day.
Toxicology: Preclinical safety data: In laboratory animals, the effects of drospirenone and ethinylestradiol were confined to those associated with the recognised pharmacological action. In particular, reproduction toxicity studies revealed embryotoxic and fetotoxic effects in animals which are considered as species specific.