Norcolut Mechanism of Action

Pharmacotherapeutic group: Sex hormones and modulators of the genital system; Progestogens. ATC code: G03DC02.
Pharmacology: Pharmacodynamics: Norethisterone is a synthetic progestogen of the 19-nortestosterone group and has similar effects to those of natural progesterone, including suppression of gonadotropins, ovulation inhibition and endometrial transformation. Norethisterone is a first-generation progestin of low progestational and slight oestrogenic activity. It has weak androgenic properties.
Pharmacokinetics: Absorption: Norethisterone is well absorbed from the intestinal tract. Its absolute bioavailability ranged from 47% to 73%.
Distribution: Norethisterone is extensively binding to proteins: 61% to albumin and 36% to sex hormone binding globulin (SHBG).
Biotransformation: Norethisterone is metabolized in the liver via hydroxylation mainly by CYP3A4.
After the deacetylation of norethisterone acetate to norethisterone, norethisterone undergoes hepatic reduction and conjugation. 5-alpha-reductase plays an important role in the metabolism of norethisterone. Since norethisterone is partially metabolized via hydroxylation by CYP3A4, inhibitors and inducers of CYP3A4 can significantly alter circulating levels of norethisterone.
The most important metabolites of norethisterone are several isomers of 5-alpha-dihydro-norethisterone and tetrahydro-norethisterone, which are excreted mainly as glucuronide conjugates. Norethisterone and some of its metabolites are conjugated by the 17-beta-hydroxy group. Low serum ethinyloestradiol levels have been measured in postmenopausal women, following oral administration of relatively large doses of norethisterone acetate or norethisterone. On the basis of AUCs determined for ethinyloestradiol and norethisterone, it was shown that the mean conversion ratio of norethisterone to ethinyloestradiol was 0.7% and 1.0% at doses of 5 and 10 mg, respectively. This results in an equivalent dose of about 4-6 micrograms ethinyloestradiol per 1 mg of orally administered norethisterone or norethisterone acetate.
Elimination: The half-life of norethisterone is around 8 to 9 hours, its peak time is around 2 hours (varies by dose and use of concomitant oestrogen). The majority of norethisterone is excreted via urine (>50% as metabolites) and faeces (20% to 40% as metabolites).