Pregina Mechanism of Action

Pharmacologic Category: Ovulation Inducing Medicine.
Pharmacology: Pharmacodynamics: Clomifene citrate is a nonsteroidal agent which may induce ovulation in appropriately selected anovulatory women. It has both estrogenic and anti-estrogenic properties but its precise mechanism of action in inducing ovulation has not been determined.
Clomifene citrate appears to stimulate the release of the pituitary gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), either from direct stimulation of the hypothalamic-pituitary axis by competing with endogenous estrogens of the uterus, pituitary or hypothalamus. This results in development and maturation of the ovarian follicle ovulation and subsequent development and function of the corpus luteum.
Clomifene citrate may also directly affect the biosynthesis of ovarian hormones. Clomifene has no progestational, androgenic or anti-androgenic effects and does not appear to interfere with pituitary-adrenal or pituitary-thyroid function.
Pharmacokinetics: Clomifene is readily absorbed from the gastrointestinal tract after oral administration. Blood concentrations of the drug are low and exhibit interpatient variation in studies using radiolabeled clomifene citrate. The volume of distribution and plasma protein binding of clomifene citrate is unknown. The E-isomer is reported to be less well absorbed and more rapidly eliminated than the Z-isomer.
Clomifene citrate is metabolized in the liver and slowly excreted via the bile. The biological half-life is reported to be 5 days although traces are found in the feces for up to 6 weeks. Mean urinary excretion is approximately 8% and fecal excretion is about 42%.
Limited studies suggest that the drug is excreted slowly from a sequestered enterohepatic recirculation pool or may be stored in body fat and subsequently released slowly.