Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1     Pharmacodynamic properties

PROGESTOGENS AND ESTROGENS IN FIXED COMBINATION
ATC Code G03AA10 (genitourinary system and sex hormones).

Single-phase estrogen-progestogen combination. Non-corrected Pearl index: 0.24 (21,521 cycles).
Minesse is a combination oral contraceptive (COC) containing ethinyl estradiol (EE) and gestodene.
COCs have been shown to exert their effect by decreasing gonadotropin secretion to suppress ovarian activity. The resulting contraceptive effect is based on various mechanisms, the most important of which is the inhibition of ovulation.

Pharmacokinetic Properties

5.2     Pharmacokinetic properties

Ethinylestradiol:
Absorption
Ethinylestradiol is rapidly and completely absorbed after oral ingestion. After administration of 15 µg, peak plasma concentrations of 30 pg/mL are reached after 1- 1.5 hours. Ethinylestradiol undergoes an extensive first pass effect, which displays great interindividual variation. The absolute bioavailability is approximately 45%.

Distribution
Ethinylestradiol has an apparent volume of distribution of 15 L/kg and binding to plasma proteins is approximately 98%. Ethinylestradiol induces the hepatic synthesis of sex-hormone binding globulins (SHBG) and corticoid-binding globulins (CBG). During treatment with 15 µg ethinylestradiol the plasma concentration of SHBG increases from 86 to about 200 nmol/L.

Biotransformation
Ethinylestradiol is metabolised completely (metabolic plasma clearance approximately 10 mL/min/kg). The metabolites formed are excreted in the urine (40%) and feces (60%).
In vitro, ethinylestradiol is a reversible inhibitor of CYP2C19, CYP1A1 and CYP1A2 as well as a mechanism based inhibitor of CYP3A4/5, CYP2C8, and CYP2J2.

Elimination
The elimination half-life of ethinylestradiol is approximately 15 hours. 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.
Page 15 of 18                                     2022-0081366
Steady state conditions
Steady state conditions are reached during the second half of the treatment cycle and serum levels of ethinylestradiol accumulate by a factor of about 1.4 to 2.1.

Gestodene:
Absorption
After oral administration gestodene is rapidly and completely absorbed. The absolute bioavailability is about 100%. After oral intake of a single 60 µg gestodene dose, peak plasma concentrations of 2 ng/mL are reached in about 60 minutes. The plasma concentrations are strongly dependent on the SHBG concentrations.

Distribution
Gestodene has an apparent volume of distribution of 1.4 L/kg following a single 60 g dose. It is 30% bound to plasma albumin and 50 – 70% bound to SHBG.

Biotransformation
Gestodene is extensively metabolised by the steroid metabolic pathway. The metabolic clearance is about 0.8 mL/min/kg following a single 60 g dose. The non-active metabolites formed are excreted in urine (60%) and faeces (40%).

Elimination
The apparent elimination half-life of gestodene is about 13 hours. The half-life is prolonged to 20 hours after concomitant administration with ethinylestradiol.

Steady state conditions
After multiple dosing concomitantly with ethinylestradiol the plasma concentration increases approximately by a factor of 2-4.