米非司酮黄体期用药对垂体－肾上腺轴的影响

Effects of Mifepristone on Pituitary-Adrenal Axis in Women Administered in Luteal Phase

征集健康育龄妇女９例于连续若干周期的黄体晚期单次口服米非司酮，剂量分别依次为２５ｍｇ、１００ｍｇ、４００ｍｇ和６００ｍｇ，并于服药前以及服药后４、８、１２、２４、４８、７２、９６和１２０ｈ采血，以测定血清ＡＣＴＨ和皮质醇。另征集健康育龄妇女１５例，随机分成三组（组Ⅰ～Ⅲ），分别在黄体早、中、晚期给于米非司酮２５ｍｇｑ１２ｈ×６，在ｄ１～ｄ７期间每天采血以测定血清ＡＣＴＨ、皮质醇和米非司酮水平。结果显示米非司酮２５ｍｇ和１００ｍｇ单次口服对ＡＣＴＨ、皮质醇水平及其昼夜分泌节律并无明显影响，可是一次口服高剂量（４００ｍｇ和６００ｍｇ）后，ＡＣＴＨ和皮质醇上午分泌水平增加，昼夜变化幅度明显减少。米非司酮多次用药（２５ｍｑｑ１２ｈ×６）期间，每天上午ＡＣＴＨ和皮质醇几乎无明显变化，黄体期早、中、晚期服药的对象，其血药浓度、ＡＣＴＨ与皮质醇水平均无明显差异。本研究提示对于非妊娠妇女，米非司酮以剂量－依赖的方式显示其抗糖皮质激素活性，只有一次口服大剂量米非司酮才会明显影响其ＡＣＴＨ与皮质醇的昼夜分泌节律。黄体期不同的生殖激素状态对口服米非司酮后的药物吸收及其抗糖皮质激素活性无明显影响。

Nine healthy women of fertile age were administered orally with mifepristone 25,100,400and 600mg in one single dose respectively in late luteal phase of 4 successive cycles,and received blood sampling before treatment and 4,8,12,24,48,72,96 and 120 h after treatment for determination of serum ACTH and cortisol levels.In addition, fifteen healthy fertile women were divided Into three groups at random and administered with mifepristone 25mg q12h×6 respectively in early,mid-and late luteal phase of one cycle,blood samples were taken each morning for measurement of ACTH,cortisol as well as mifepristone levels.The results showed that mifepristone 25 and 100mg in single dose had no effects on serum levels of ACTH、cortisol and their diurnal rhythms,while one single high dose(400 or 600mg)of the compound induced marked increase in ACTH and cortisol levels with significant reduction of their diurnal changes.In contrast,serum ACTH,cortisol and mifepristone levels had no significant changes after administration of the compound in multiple low doses during various period of luteal phase.The results of this study indicated that mifepristone presented its antiglucocorticoid activity in dose-dependent mannar,one single high dose of mifepristone(400mg or more)affected the diurnal rhythms of ACTH and cortisol secretion,and there were no significant differences in absorption and effects on pituitary-adrenal axis of the compound used in different periods of luteal phase.