Cybelle Mechanism of Action

Pharmacology: Pharmacodynamics: Cyproterone acetate is a competitive antagonist on the androgen receptor, has inhibitory effects on the androgen-synthesis in target cells and produces a decrease of the androgen blood concentration through an antigonadotropic effect. This antigonadotropic effect is amplified by ethinylestradiol which up-regulates as well the synthesis of Sexual-Hormone-Binding-Globulin (SHBG) in plasma. It thereby reduces free, biologically available androgen in the circulation.
Pharmacokinetics: Cyproterone acetate: Absorption: Orally administered cyproterone acetate is rapidly and completely absorbed. Peak serum concentrations of 15ng/ml are reached at about 1.6 hours after single ingestion. Bioavailability is about 88%.
Distribution: Cyproterone acetate is almost exclusively bound to serum albumin. Only 3.5-4.0% of the total serum drug concentrations are present as free steroid. The ethinylestradiol-induced increase in SHBG does not influence the serum protein binding of cyproterone acetate. The apparent volume of distribution of cyproterone acetate is about 986±437L.
Metabolism: Cyproterone acetate is almost completely metabolized. The main metabolite in plasma was identified as 15β-OH-CPA which is formed via the cytochrome P450 enzyme CYP3A4. The clearance rate from serum is about 3.6 ml/min/kg.
Elimination: Cyproterone acetate serum levels decrease in two phases which are characterized by half-lives of about 0.8 h and about 2.3-3.3 days. Cyproterone acetate is partly excreted in unchanged form. Its metabolites are excreted at a urinary to biliary ratio of about 1:2. The half-life of metabolite excretion is about 1.8 days.
Steady-state conditions: Cyproterone acetate pharmacokinetics is not influenced by SHBG levels. Following daily ingestion drug serum levels increase about 2.5-fold reaching steady-state conditions during the second half of a treatment cycle.
Ethinylestradiol: Absorption: Orally administered ethinylestradiol is rapidly and completely absorbed. Peak serum concentrations of about 71pg/ml are reached at 1.6 hours. During absorption and first-liver passage, ethinylestradiol is metabolized extensively, resulting in a mean oral bioavailability of about 45% with a large interindividual variation of about 20-65%.
Distribution: Ethinylestradiol is highly but non-specifically bound to serum albumin (approximately 98%), and induces an increase in the serum concentrations of SHBG. An apparent volume of distribution of about 2.8-8.6 l/kg was determined.
Metabolism: Ethinylestradiol is subject to presystemic conjugation in both small bowel mucosa and the liver. Ethinylestradiol is primarily metabolized by aromatic hydroxylation but a wide variety of hydroxylated and methylated metabolites are formed, and these are present as free metabolites and as conjugates with glucuronides and sulfate. The clearance rate was reported to be about 2.3-7 ml/min/kg.
Elimination: Ethinylestradiol serum levels decrease in two disposition phases characterized by half-lives of about 1 hour and 10-20 hours, respectively. Unchanged drug is not excreted, ethinylestradiol metabolites are excreted at a urinary to biliary ratio of 4:6. The half-life of metabolite excretion is about 1 day.
Steady-state conditions: Steady-state conditions are reached during the second half of a treatment cycle when serum drug levels are higher by 60% as compared to single dose.