ミフェプリストン 化学特性,用途語,生産方法
外観
白色～うすい黄色～緑色粉末～結晶
用途
ミフェプリストン (mifepristone) は、抗グルココルチコイド作用と抗アンドロゲン作用も持つ薬物。通常、ミソプロストールとの併用により使用される。妊娠7週（49日；受精からは5週間相当）以内の初期であれば胎児は膣から血塊となって排出され中絶される。
効能
妊娠中絶薬, 避妊薬, プロゲステロン受容体拮抗薬
説明
Mifepristone is an orally-active progesterone and glucocorticoid receptor antagonist
indicated for use as a post-coital contraceptive. In addition to being an abortifacient,
mifepristone is reported to be effective in the treatment of ocular hypertension; its
potential therapeutic effect in hormone-dependent tumors is currently under investigation.
化学的特性
Pale Yellow Solid
使用
Mifepristone is a progesterone receptor antagonist with partial agonist activity. Abortifacient.
適応症
Mifepristone is a progesterone receptor antagonist that
has a high affinity for glucocorticoid receptors and little
agonist effect.This drug has recently been approved for
use in the United States for the treatment of hypercortisolism.
At high doses, mifepristone blocks negative
feedback of the hypothalamic–pituitary axis, thereby increasing
endogenous corticotrophin and cortisol levels.
Because mifepristone exerts its effects at the receptor
level and not by altering glucocorticoid production, elevated
serum cortisol and corticotrophin levels may not
accurately reflect the effectiveness of the therapeutic
regimen. Mifepristone does not inhibit cortisol binding
to the mineralocorticoid receptor, so that the resulting
corticotrophin disinhibition may cause potassium depletion.
Thus, administration of a mineralocorticoid receptor
antagonist such as spironolactone may be indicated
with mifepristone. Hypoadrenalism, nausea, and
drowsiness have been reported during prolonged administration
of mifepristone.
世界保健機関（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.
生物活性
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.
薬物動態学
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.
臨床応用
An antiprogestin is a substance that competes with progesterone for its receptor and, ultimately, prevents progesterone from binding to and activating its receptor. Because progesterone is integral to the continuation of an early pregnancy, it is expected that antipro-gestins will interfere with pregnancy maintenance. In 1982, the first antiproges tin, mifepristone (RU 486), was reported. Mifepristone was shown to interrupt early stages of implantation and pregnancy in humans.
参考文献
https://pubchem.ncbi.nlm.nih.gov/compound/mifepristone#section=Top
https://www.drugbank.ca/drugs/DB00834
https://www.drugs.com/cdi/mifepristone-tablets.html
ミフェプリストン 上流と下流の製品情報
原材料
準備製品