长期使用复方炔诺酮庚酸酯后炔诺酮的药代动力学及体内蓄积

Pharmacokinetics and Possible Accumula-tion of NET after Long-Term Use of Com-bined Contraceptive Injectable of Norethis- terone Enanthate with Estradipl Valerate.

17例健康育龄妇女连续每月肌注一次复方炔诺酮庚酸酯避孕针(炔诺酮庚酸酯50mg/戊酸雌二醇5mg)共12个月。于用药第1、6和12个月的临注射前和注射后不同时间取血,用放射免疫法测定血清中炔诺酮水平。在第1、6、12次肌注后,血中炔诺酮(NET)水平分别于5.5±1.2、5.1±1.3和5.0±1.4天达到峰值,平均血药峰值浓度为8.62±2.53、5.74±1.91和5.90±1.23ng/ml。个体间Cm_(ax)可有3.4倍的差异。三次肌注后NET的体内平均滞留时间MRT为9.1±0.7、9.75±1.0和9.6±1.1天;肌注后28天血清NET浓度分别为0.64±0.36、0.90±0.39和0.67±0.29ng/ml。第1、6和12次注射后药时曲线下面积(AUC)逐步减小,分别为97.8+24.5、84.65±21.3和77.6±15.1ng/ml/d。研究结果表明,肌注复方炔诺酮庚酸酯后NET的药代动力学有明显的个体差异;首次肌注后Cm_(ax)、AUC大于第6和12次肌注后值,可能与用药后性激素结合球蛋白水平变化有关,但上述参数在第6和12次给药后未见明显差别。本文结果提示连续使用复方炔诺酮庚酸酯避孕针并不引起对象体内NET蓄积。

Seventeen healthy fertile women received continuously muscular injection of once-a-month combined contraceptive norethisterone enanthate 50mg plus estradi-ol valerate 5mg for 12 months. Blood samples were collected immediately before and 1,3,5,7,14,21,28 days after the 1st,6th and 12th injection. Serum NET levels were measured by RIA. The mean time of serum NET reaching peak valuesing after 1st, 6th and 12th were 5. 5±1. 2,5. 1±1. 3 and 5. 0 ± 1. 4 days; the mean Cmax were 8. 62 ± 2.53,6. 74±1. 91 and 5. 90±1. 24 ng/ml, showing 3-4 fold individual difference. After the 1st,6th and 12th injection,mean residence time (MRT) of NET were 9. 1 ± 0. 7, 9. 7 ± 1. 0 and 9. 6 ± 1. 1 days; serum NET concentrations at day 28 were 0. 64 ± 0. 36,0. 90±0. 39 and 0. 67±0. 29 ng/ml; the AUC of NET were 97. 8±24. 5,84. 6± 21. 3 and 77. 6± 15. 1 ng/ml. The results showed that Cmax and AUC values decreased significantly between .the 1st and 6th injections, which may be related to the variation of SHBG after long-term use of this combined contraception. The results from this study indicated that there was no accumulation of NET after long-term treatment with norethisterone enanthate and estradiol valerate.