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
Gestodene and ethinylestradiol have estrogenic and progestogenic peripheral effects.
The contraceptive effect of gestodene and ethinylestradiol 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.
Orally administered gestodene is rapidly and completely absorbed. Peak serum concentrations of 4 ng/ml are reached at about 1 hour after single ingestion. Bioavailability is about 99%.
Gestodene is bound to serum albumin and to sex hormone binding globulin (SHBG). Only 1 to 2% of the total serum gestodene concentration is present as free steroid, 50 to 70% is specifically bound to SHBG. The ethinylestradiol-induced increase in SHBG influences the distribution over 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 l/kg.
Gestodene is completely metabolised by the known pathways of steroid metabolism. The metabolic clearance rate from the serum is 0,8 ml/min/kg. No interaction was found with the coadministered ethinylestradiol.
Gestodene serum levels decrease in two phases. The terminal disposition phase is characterised by a half-life of 12 to 15 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 by ethinylestradiol. Following daily ingestion, gestodene serum levels increase about four-fold reaching steady-state 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 first-pass 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 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 ml/min/kg.
Ethinylestradiol serum levels decrease in two phases. The terminal disposition phase is characterised by a half-life of approximately 24 hours. Unchanged ethinylestradiol is not excreted, 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 are reached after 3 to 4 days when serum ethinylestradiol levels are higher by 30 to 40% as compared to single dose.
None.
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