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32例月经正常的健康育龄妇女随机分为四组,每组8人。分别每月一次肌注避孕药庚炔诺酮(NET-OEN)50mg配伍戊酸雌二醇(EV)5mg(组1)、NET-OEN25mg配伍EV2.5mg(组2)、NET-OEN50mg(组3)和NET-OEN25mg(组4),共3个月。于第3个给药周期及2个随访周期中每周3次取外周血样,用放射免疫法测定血中炔诺酮(NET)、雌二醇及孕酮水平。各组血中NET浓度的平均(几何均值,下同)达峰时间分别为4.8、4.4、6.7、及3.4天,平均峰值浓度依次为15.90、7.88、12.58和8.01nmol/l,均显示有明显个体差异。各组血浆炔诺酮的表现消除半衰期分别为18.2、15.3、18.8与13.9天。给药后30天血中NET浓度仍分别有2.75、1.35、2.48和1.39nmol/l。EV对NET的药代动力学过程并无明显影响。组1及组2的外源性雌二醇平均峰值分别为1520和954pmol/l,持续时间为13.1和12.3天,提示戊酸雌二醇剂量不宜再进一步减低。四组出现首次内源性雌二醇峰值的平均时间依次为52、41、49和15天。各组首次出现孕酮升高的平均时间为76、53、64和48天。末次给药后至84天,各组发生排卵例数为4/8、6/8、4/8和6/8。表明配伍EV后具有更长的抑制排卵及黄体形成作用。各组月经分析结果表明,使用雌-孕激素复方制剂组的月经情况优于单纯NET组,组1的月经情况最佳。各组用药后HDL—C均无显著变化,仅组1在用药3次后HDL—C水平较用药前显著为低,但在停药1个周期后即迅速恢复。
32 healthy women of childbearing age with normal menstruation were randomly divided into four groups with 8 in each group. The mice were treated with NET-OEN 50mg (EV) 5mg (group 1), NET-OEN25mg with EV2.5mg (group 2) and NET-OEN50mg 3) and NET-OEN25mg (Group 4) for 3 months. Peripheral blood samples were taken 3 times a week in the 3rd dosing cycle and 2 follow-up cycles, and the blood levels of norethindrone (NET), estradiol and progesterone were measured by radioimmunoassay. The mean (geometric mean, same below) peak concentrations of NET in each group were 4.8, 4.4, 6.7 and 3.4 days, respectively. The average peak concentrations were 15.90, 7.88, 12.58 and 8.01 nmol / Individual Differences. The elimination half-life of plasma norethindrone was 18.2, 15.3, 18.8 and 13.9 days in each group. 30 days after administration of blood NET concentrations were still 2.75,1.35,2.48 and 1.39nmol / l. EV has no significant effect on the pharmacokinetics of NET. The mean peak exogenous estradiol concentrations in Groups 1 and 2 were 1520 and 954 pmol / l, respectively, for durations of 13.1 and 12.3 days, suggesting that estradiol valerate should not be further reduced. The average time to first peak of endogenous estradiol in the four groups was 52, 41, 49 and 15 days. The mean time for the first rise in progesterone in each group was 76, 53, 64, and 48 days. From the last administration to 84 days, the number of ovulation in each group was 4/8, 6/8, 4/8 and 6/8. It shows that the compatibility of EV has a longer inhibit ovulation and luteal formation. The results of menstruation in each group showed that menstruation was better than that of the pure NET group in the combination of estrogen and progestin, and group 1 had the best menstruation. There was no significant change of HDL-C in each group after treatment, only HDL-C level of group 1 was significantly lower than that before treatment after 3 times of treatment, but recovered rapidly after 1 cycle of treatment.