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
MELODENE is a combined low-dose monophasic oral contraceptive with estrogenic (ethinylestradiol) and progestogenic (gestodene) peripheral effects.
The contraceptive effect of MELODENE 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 3,5 ng/ml are reached at about 1 hour after single dose 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 concentrations are present as free steroid, 50 to 70% are specifically bound to SHBG. The ethinylestradiol-induced 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 l/kg.
Gestodene is completely metabolised by the known pathways of steroid metabolism. The clearance rate from serum is 0,8 ml/min/kg. No interaction was found with the co-administered ethinylestradiol.
Gestodene serum levels decrease in two phases. The terminal disposition phase is characterised by a half-life of approximately 12 hours. Gestodene is not excreted in its unchanged form. Its metabolites are excreted at a urinary to biliary ratio of about 6:4. The half-life of metabolite excretion is about 24 hours.
Gestodene pharmacokinetics are influenced by SHBG levels, which are increased about two-fold when co-administered with 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 65 pg/ml are reached at 1,7 hours. During absorption and first liver passage, ethinylestradiol is metabolised extensively, resulting in a mean oral bioavailability of about 45% with a large interindividual variation of about 20 to 65%.
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 to 8,6 l/kg was reported.
Ethinylestradiol is subject to presystemic conjugation in both the 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 clearance rate was reported to be 2,3 to 7 ml/min/kg.
Ethinylestradiol serum levels decrease in two disposition phases characterised by half-lives of about 1 hour and 10 to 20 hours, respectively. Unchanged ethinylestradiol is not excreted; ethinylestradiol metabolites are excreted at a urinary to biliary ratio of 4:6. The half-life of metabolite excretion is about 24 hours.
According to the variable half-life of the terminal disposition phase from serum and the daily ingestion, steady-state serum levels of ethinylestradiol will be reached after about 1 week.
None.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
