SERUM PHARMACOKINETICS OF ORALLY-ADMINISTERED DESOGESTREL AND BINDING OF CONTRACEPTIVE PROGESTOGENS TO SEX-HORMONE BINDING GLOBULIN
SERUM PHARMACOKINETICS OF ORALLY-ADMINISTERED DESOGESTREL AND BINDING OF CONTRACEPTIVE PROGESTOGENS TO SEX-HORMONE BINDING GLOBULIN
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DOI：
10.1016/0002-9378(90)90553-j
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发表时间：
1990-12-01
影响因子：
9.8
通讯作者：
QVIST, I
中科院分区：
文献类型：
--
作者：
BERGINK, W;ASSENDORP, R;QVIST, I
用放射免疫法测定了25例女性患者服用地塞米松(0.150 mg)和雌二醇(0.030 mg)两种片剂后21天的血清3-酮雌孕酮和乙炔雌二醇水平。地塞米松的药代动力学参数为：(1)最大血药浓度，(2)达到最大血药浓度的时间，(3)血药浓度-时间曲线下的总面积，(4)血清消除半衰期。这些参数的个体间差异与观察到的其他避孕药组合的个体间差异相似，这些避孕药包含乙炔雌二醇和去甲孕酮、左旋诺孕酮或孕二烯。避孕孕激素的血清分布是由它们与性激素结合球蛋白的亲和力和性激素结合球蛋白的浓度决定的。我们分析了决定与性激素结合球蛋白结合的结构特征。18-甲基增加，11-亚甲基减弱与性激素结合球蛋白的结合。只有当与18-甲基结合时，C-15上的双键才能加强结合。因此，与性激素结合球蛋白的结合力比3-酮地格孕酮和3-酮-地孕酮强得多。
Serum levels of 3-ketodesogestrel and ethinyl estradiol were analyzed by radioimmunoassay in a balanced crossover study with two tablet formulations containing desogestrel (0.150 mg) and ethinyl estradiol (0.030 mg) in 25 women under steady-state conditions after 21 days of treatment. The pharmacokinetic properties of desogestrel were characterized by the following parameters: (1) maximum serum concentration, (2) time to maximum serum concentration, (3) total area under the serum concentration versus time curve, and (4) serum half-life of elimination. The interindividual variation in these parameters was comparable with that observed with other contraceptive combinations containing ethinyl estradiol and norethisterone, levonorgestrel, or gestodene. The serum distribution of contraceptive progestogens is known to be determined by their affinity to sex hormone-binding globulin and the concentration of sex hormone-binding globulin. We analyzed the structural features that determine binding to sex hormone-binding globulin. The 18-methyl group increased and the 11-methylene group weakened the binding to sex hormone-binding globulin. The double bond at C-15 reinforced the binding only when combined with an 18-methyl group. Therefore, the binding of levonorgestrel (the 18-methyl derivative of norethisterone) and gestodene (the DELTA-15, 18 methyl derivative of norethisterone) to sex hormone-binding globulin was much stronger than that of 3-keto-desogestrel and norethisterone.