Sarkar N N
Department of Reproductive Biology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi.
Int J Clin Pract. 2002 Mar;56(2):140-4.
This article reviews the development of mifepristone (RU486) as a female contraceptive drug. Mifepristone is an orally active compound with nearly 40% bioavailability after first pass effect. The steady plasma level of mifepristone ranges from 65 nmol/l with 1 mg/day to 1 micromol/l with 10 mg/day and reaches 2.5 micromol/l, 4.5 micromol/l and 5.4 micromol/l with mifepristone 50 mg, 100 mg and 200 mg daily, respectively, over the treatment period. Inhibition of ovulation may be achieved at serum mifepristone concentration of 232.7 nmol/l. Mifepristone appears to antagonise progesterone at the pituitary level to suppress gonadotropin and steroid hormone secretion rather than to act primarily on the hypothalamus to delay or inhibit ovulation. In fact, the endometrium is most sensitive to mifepristone. Low-dose mifepristone impairs luteal phase endometrial development and receptivity by altering endometrial parakine, cytokine and enzyme activity. Thus, low-dose mifepristone can significantly reduce the rate of conception without inhibiting ovulation. However, further research is needed to standardise the dose and dose-schedule to achieve the desired efficacy of low-dose mifepristone for routine clinical use with minimal or no side-effects.
本文综述了米非司酮（RU486）作为一种女性避孕药的发展情况。米非司酮是一种口服活性化合物，首过效应后生物利用度近40%。米非司酮的稳态血浆水平在每日1mg时为65nmol/l，每日10mg时为1μmol/l，在治疗期间，每日服用米非司酮50mg、100mg和200mg时，分别达到至2.5μmol/l、4.5μmol/l和5.4μmol/l。血清米非司酮浓度达到232.7nmol/l时可能会抑制排卵。米非司酮似乎在垂体水平拮抗孕酮，以抑制促性腺激素和类固醇激素分泌，而不是主要作用于下丘脑来延迟或抑制排卵。事实上，子宫内膜对米非司酮最为敏感。低剂量米非司酮通过改变子宫内膜旁分泌因子、细胞因子和酶活性，损害黄体期子宫内膜发育和容受性。因此，低剂量米非司酮可在不抑制排卵的情况下显著降低受孕率。然而，需要进一步研究来规范剂量和给药方案，以实现低剂量米非司酮在常规临床使用中具有最小或无副作用的预期疗效。
