Source: Health Products Regulatory Authority (ZA) Revision Year: 2022 Publisher: Bayer (Pty) Ltd, Reg. No.: 1968/011192/07, 27 Wrench Road, Isando 1609
Pharmacotherapeutic group (ATC): Progestogens and estrogens, fixed combinations
ATC Code: G03AA
MIRELLE is a low-dose monophasic ovulation controlling agent with estrogenic and progestogenic peripheral effects.
The mode of action of gestodene in combination with ethinylestradiol includes:
Orally administered gestodene is rapidly and completely absorbed. Peak serum concentrations of 4 ng/ml is reached at about 1 hour after single ingestion. Bioavailability is approximately 99%.
Gestodene is bound to serum albumin and to sex hormone binding globulin (SHBG). Only 1 to 2% of the total serum concentration is present as free steroid, 50 to 70% is specifically bound to SHBG. The ethinylestradiolinduced increase in SHBG influences the proportion of gestodene bound to the serum proteins, causing an increase of the SHBG-bound fraction and a decrease of the albumin-bound fraction. The apparent volume of distribution of gestodene is 0,7 to 1,4 l/kg.
Gestodene is completely metabolised by the known pathways of steroid metabolism. The metabolic clearance rate from the serum is 0,8 to 1,0 ml/min/kg. When gestodene was acutely coadministered with ethinylestradiol, no direct interaction was found.
Gestodene serum levels decrease in two phases. The terminal disposition phase is characterised by a half-life of 12 to 20 hours. Gestodene is not excreted in unchanged form. Its metabolites are excreted at a urinary to biliary ratio of about 6:4. The half-life of metabolite excretion is about 1 day.
Gestodene pharmacokinetics are influenced by SHBG levels, which are increased threefold when coadministered with ethinylestradiol. Following daily ingestion, serum gestodene levels increase about four-fold reaching steadystate conditions during the second half of a treatment cycle.
Orally administered ethinylestradiol is rapidly and completely absorbed. Peak serum concentrations of about 80 pg/ml are reached within 1 to 2 hours. Absolute bioavailability as a result of presystemic conjugation and firstpass metabolism is approximately 60%.
Ethinylestradiol is highly but non-specifically bound to serum albumin (approximately 98,5%) and induces an increase in the serum concentrations of SHBG. An apparent volume of distribution of about 5 to 18 l/kg was determined.
Ethinylestradiol is subject to presystemic conjugation in both small bowel mucosa and the liver. Ethinylestradiol is primarily metabolised 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 sulphate. The metabolic clearance rate is about 5 to 13 ml/min/kg.
Ethinylestradiol serum levels decrease in two phases, the terminal disposition phase is characterised by a half-life of approximately 16 to 24 hours. Only metabolites of ethinylestradiol are excreted occurring at a urinary to biliary ratio of 4:6. The half-life of metabolite excretion is about 1 day.
Steady-state conditions are reached after 3 to 4 days when serum ethinylestradiol levels are higher by 30 to 40% as compared to single dose.
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