4- Mifepristone

Mifepristone. After oral adininistration, peak plasma levels of mifepristone (84) (RU 486) are reached in 1 h and over 95% was bound to plasma proteins (351,352). The plasma half-life of RU 486 is approximately 24 h (352,353). In humans, monodemethylated (98), didemethylated (99) and alcohoHc nondemethylated (100) metaboHtes of RU 486 have been identified (351). These metaboHtes show some progestin-binding affinity, approximately five to ten times lower than that of RU 486 itself. RU 486 and its metaboHtes can be measured by radioimmunoassay and hplc (353,354). 

Antiprogestins are progesterone receptor antagonists such as mifepristone (RU 38486), ORG 31710, ZK137 316, ZK 230 211, ZK98299 (Onapristone). 

Megestrol acetate—has glucocorticoid-like activity ° Mifepristone (RU 486)—antagonizes glucocorticoid receptors... 

Mifepristone Antagonizes Up to 20 mg/kg Gl intolerance, rash, Requires cautious use since few... 

Tebar M, Bellido C, Aguilar R, Sanchez-Criado JE (1994) Inappropriate ovarian feedback in basal gonadotropin secretion in 4-day cyclic rat treated with mifepristone role of endogenous estradiol. J Endocrinol Invest 17 425-430... 

Mifepristone Good Mild hot flashes Os Long term Low... 

Like the medical treatment of uterine leiomyomas, danazol, gestrinone, mifepristone, and GnRH-a, with or without add-back therapy, have been proposed for the treatment of endometriosis as well (Olive et al. 2001 Stones et al. 2004), but unlike leiomyomas, oral contraceptive pills, in cyclic or continuous administration, and medroxyprogesterone acetate also seem to be effective (Olive et al. 2001 Stones et al. 2004). A significant benefit in terms of pelvic pain relief also is obtained with the use of nonsteroidal anti-inflammatory drugs (Olive et al. 2001 Stones et al. 2004). 

An anti-progesterone (mifepristone, RU 486) pill is used to inhibit ovulation and implantation. 

To date, the results of five phase II clinical trials with PR antagonists in patients with metastatic breast cancer have been reported [191]. In postmenopausal women, two studies with mifepristone as second- or third-hne treatment for metastatic breast cancer showed an objective response rate (complete response plus partial response) of 10 and 13% and stable disease in 54 and 40% of patients, respectively. A third study was conducted using mifepristone as first-line treatment. An objective response rate of 11% and a stable disease rate of 39% was reported [191]. 

Pregnancy term/naf/on- Misoprostol has been used in combination with mifepristone for pregnancy termination. Patients taking mifepristone must take 400 meg misoprostol orally 2 days after taking mifepristone unless a complete abortion has already been confirmed before that time. 

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