Mifepristone

Description

Mifepristone is a progestational and glucocorticoid hormone antagonist with various medical applications. In the context of Cushing's syndrome, it reduces the effects of excess cortisol without causing decreased cortisol production. Additionally, mifepristone is employed to terminate pregnancies by acting as a progesterone receptor antagonist, inducing bleeding during the luteal phase and early pregnancy. As an antiprogestin, mifepristone competes with progesterone for its receptor, preventing progesterone from activating the receptor and interfering with early pregnancy maintenance. It was the first antiprogestin reported in 1982 and has shown efficacy in interrupting early stages of implantation and pregnancy in humans. Additionally, mifepristone has been explored for its glutamate uptake inhibition and AMPA-blocking properties.

Chemical Properties

Pale Yellow Solid

Originator

Roussel-Uclaf (France)

Uses

Primarily used for the treatment of hypercortisolism in patients with nonpituitary Cushing syndrome, mifepristone interferes with the binding of cortisol to its receptor. The drug has been approved in the United States for treating hypercortisolism. At high doses, mifepristone blocks negative feedback of the hypothalamic–pituitary axis, increasing endogenous corticotrophin and cortisol levels. It does not inhibit cortisol binding to the mineralocorticoid receptor, necessitating caution to address potential potassium depletion by using a mineralocorticoid receptor antagonist like spironolactone. Prolonged administration may lead to hypoadrenalism, nausea, and drowsiness.

Brand name

Mifeprex (Danco);Ru-486;Mifegyne.

Therapeutic Function

Antiprogesterone

World Health Organization (WHO)

Mifepristone, an antiprogesterone used in combination with a prostaglandin for the termination of early pregnancy, was introduced in 1990. Use of the combination has been associated with episodes of coronary spasm that are attributed to administration of the prostaglandin and which have resulted in several cases of cardiac infarction and ventricular fibrillation. At least one of these incidents has been fatal.

Biological Activity

Selective antagonist at progesterone (PR) and glucocorticoid (GR) receptors in vitro and in vivo . Is a silent antagonist at PR and has a higher affinity than progesterone. Has higher affinity for GR than dexamethasone.

Biochem/physiol Actions

Therefore, mifepristone is considered to be a potent abortifacient. It is also known to inhibit human chorionic gonadotropin. Mifepristone results in decidual necrosis.

Pharmacokinetics

Following oral administration, mifepristone is rapidly absorbed, with a peak plasmaconcentration in approximately 90 minutes , an oral bioavailability of approximately 70%, and a term inal elimination half-life of 18 hours. It is 98% protein bound, primarily to album in and α1-acid glycoprotein. Mifepristone is metabolized primarily via CYP3A4 pathways involving mono- and di-N-demethylation and terminal hydroxylation of the 17-propynyl chain. The fact that approximately 83% of the drug is recovered in the feces and 9% in the urine suggests a biliary route of elimination. Mifepristone also demonstrates antiglucocorticoid activity.