Exluton Mechanism of Action

Pharmacology: Pharmacodynamics: Lynestrenol (Exluton) is a progestogen-only pill, which contains the progestogen lynestrenol (ATC-class G03A C02). Like other progestogen-only pills, Lynestrenol (Exluton) is best suited for use during breast-feeding and for women who may not or do not want to use estrogens.
In the body lynestrenol is converted into the biologically active metabolite norethisterone, which binds to the progesterone receptors in the target organs (e.g. the myometrium). The contraceptive effect of Lynestrenol (Exluton) is achieved primarily by increasing the viscosity of the cervical mucus, thus reducing sperm penetration. Other effects include the decreased receptivity of the endometrium to the oocyte and the disturbed transport through the tubae. Furthermore, in about 70% of the women ovulation is inhibited, as can be concluded from both the absence of the midcycle LH-peak and the absence of an increase of luteal progesterone. No clinically relevant effects on the carbohydrate metabolism, lipid metabolism and haemostasis have been observed.
The contraceptive efficacy of Lynestrenol (Exluton) approaches that of the combined OC, provided the tablets are taken in accordance with the directions of use. In comparison with the combined pill, more irregular bleeding may occur with Lynestrenol (Exluton) whereas incidentally a period may fail to occur. Generally, after a period of adaptation, bleeding pattern with the product is acceptable.
Pharmacokinetics: Lynestrenol (LYN) is a pro-drug and is metabolised into the pharmacologically active metabolite norethisterone (NET).
Absorption: After oral dosing of Lynestrenol (Exluton), LYN is rapidly absorbed and converted into NET. Peak plasma levels are reached 2-4 hours after tablet intake. Absolute bioavailability of NET is 64%.
Distribution: NET is 96% bound to plasma proteins, predominantly to albumin (61%) and to a lesser extent to SHBG (sex hormone binding globulin) (35%).
Metabolism: Phase I metabolism of LYN includes a 3-hydroxylation and subsequently a dehydrogenation. The active metabolite NET is further reduced; degradation products are conjugated to sulphates and glucuronides.
Elimination: NET is eliminated with a mean half-life of approximately 15 hours. The plasma clearance is approximately 0.6 L per hour. Excretion of LYN and its metabolites is with urine (predominantly as glucuronides and sulphates and to a lesser extent as unchanged LYN) and faeces. The ratio of urinary:faecal excretion is 1.5:1.
Toxicology: Preclinical safety data: Reproduction studies in rabbits have shown that exposure to high doses of lynestrenol during organogenesis induces abnormalities of the central nervous system. Otherwise, toxicological studies did not reveal any effects other than those, which can be explained from the hormonal properties of lynestrenol. So far, the effects perceived in animal studies have not been confirmed in humans.