title: Pharmacological properties of mifepristone: toxicology and safety in animal and human studies.
abstract: Roussel Uclaf in partnership with the INSERM unit of Prof. E.E. Baulieu first discovered mifepristone (RU486) as part of a large research program on steroidal compounds with antihormone properties. Exhibiting a strong affinity to the progesterone and the glucocorticoid receptors, mifepristone exerted competitive antagonism to these hormones both in in vitro and in animal experiments. Due to its antiprogesterone activity, it was proposed that mifepristone be used for the termination of early human pregnancy. Mifepristone, at a dose of 600 mg initially used alone, was then used with a subsequent low dose of prostaglandin that led to a success rate of 95% as a medical method for early termination of pregnancy (TOP). Its use was extended to other indications, such as cervical dilatation prior to surgical TOP in the first trimester, therapeutic TOP for medical reasons beyond the first trimester, and for labor induction in case of fetal death in utero. The efficacy and safety of this treatment has been confirmed based on its use for over a decade, with close adherence to the approved recommendations. This paper describes the safety studies conducted in animals as well as the safety follow-up and side effects reported with use of the compound in various indications either approved or unapproved. The rationale for warnings and contraindications for use of the product are also explained. At lower doses, the molecule has proven promising for contraceptive purposes with few reported side effects. However, development of the product for this indication would require long-term studies. Although political and philosophical obstacles have delayed research, the use of mifepristone for other potential indications in gynecology or oncology should be investigated.
authors.affiliation: Center for Biomedical Research, Population Council Regine Sitruk-Ware Center for Biomedical Research, 1230 York Avenue, 6th Floor, New York, NY 10021, USA. regine@popcbr.rockefeller.edu
authors.forename: Regine
authors.initials: R
authors.lastname: Sitruk-Ware
authors.forename: Irving M
authors.initials: IM
authors.lastname: Spitz
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D003283:Contraceptives, Postcoital, Synthetic / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015735:Mifepristone / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D023421:Models, Animal; D011374:Progesterone / Q000037:antagonists & inhibitors; D012449:Safety
chemical_list: D003283:Contraceptives, Postcoital, Synthetic; D015735:Mifepristone; D011374:Progesterone