Pharmacology: Pharmacodynamics: Clomifene is a non-steroidal compound with weak estrogenic and moderate antiestrogenic properties. Clomifene induces ovulation by increasing the output of pituitary gonadotropins. It binds competitively to estrogen receptors, decreasing the sites available to endogenous estrogen. The decreased binding of endogenous estrogen to hypothalamic and pituitary estrogen receptors results in increased secretion of luteinizing hormone-releasing hormone (LH-RH) and follicle-stimulating hormone-releasing hormone (FSH-RH) followed by the gonadotropins LH and FSH. In females, the gonadotropins stimulate maturation and endocrine activity of the ovarian follicle which is followed by the development and function of the corpus luteum.
In a hypothetical Clomifene induced ovulatory cycle resulting in successful ovulation, the initial endocrine event is an increase in LH and FSH levels. LH and FSH levels decline following discontinuation of Clomifene, but then surge at mid-cycle. Concomitantly, a sustained increase in estradiol is seen beginning with Clomifene administration and ending at a preovulatory peak. With successful ovulation, a substantial increase in progesterone levels is seen, indicating the formation of a functional corpus luteum.
Ovulation occurs 6 to 12 days after a course of therapy.
Pharmacokinetics: Absorption: Clomifene citrate is readily absorbed from the gastrointestinal tract.
Metabolism: It is metabolised in the liver and slowly excreted via the bile. Enterohepatic circulation occurs.
Elimination: The majority of unchanged drug and its metabolites are excreted in the feces. The biological half-life is reported to be 5 days although traces are found in the faeces for up to 6 weeks. Appearance of the drug after 6 weeks suggests enterohepatic recirculation of the drug and metabolites. A small amount of unchanged drug and its metabolites is excreted in the urine and detectable for 6 weeks.