Pharmacotherapeutic group: Other sex hormone and modulator of the reproductive function/antiprogestogen. ATC code: G03XB01.
Pharmacology: Pharmacodynamics: Mifepristone is a synthetic steroid, that acts as a progesterone antagonist by competing with endogenous progesterone for receptor binding. It binds with very high affinity (2 to 10 times that of progesterone) to these receptors. The mechanism of action for emergency contraception of mifepristone includes: It disrupts the follicular maturation as well as the endocrine function of the granulosa cells, so actually the patients are far less likely to ovulate if it is taken prior to ovulation.
It disrupts the mid-cycle LH surge, again prohibiting ovulation.
If taken later in the cycle, it interrupts hormonal support to the endometrium, makes the endometrial cavity desynchronous, this leads to degeneration and shedding of the endometrial lining, thereby preventing or disrupting implantation of the conceptus. At doses ranging from 3 to 10 mg/kg orally, it inhibits the action of endogenous or exogenous progesterone in different animal species (rat, mouse, rabbit and monkey). This action is manifested in the form of pregnancy termination in rodents.
Pharmacokinetics: Absorption: After oral doses, peak plasma concentrations of mifepristone occur after about 1 to 2 hours; bioavailability is about 70%.
Distribution: Mifepristone is about 98% bound to plasma proteins, mainly α1-acid glycoprotein.
Biotransformation and elimination: Elimination is biphasic; a slow phase is followed by a more rapid terminal phase, with an elimination half-life of about 18 hours. Mifepristone undergoes hepatic oxidative metabolism, mainly by the cytochrome P450 isoenzyme CYP3A4, and metabolites are excreted in the bile and eliminated in the faeces. Only a small fraction is detected in the urine.