Zhou X F, Shao Q X, Han X J, Weng L J, Sang G W
Department of Clinical Pharmacology, Zhejiang Academy of Medical Sciences, Hangzhou, People's Republic of China.
Contraception. 1998 Jun;57(6):405-11. doi: 10.1016/s0010-7824(98)00048-1.
To provide pharmacokinetic data for safety evaluation on prolonged treatment with Cyclofem, which contains 25 mg medroxyprogesterone acetate (MPA) and 5 mg estradiol cypionate in 0.5 mL microcrystalline aqueous suspension, the pharmacokinetic profiles of MPA after single and multiple administration of this monthly injectable contraceptive were investigated in Chinese women. Nine healthy fertile women received Cyclofem based on a once-a-month regiment for up to 1 year. Blood samples were collected immediately prior to drug administration and on days 1, 3, 5, 7, 14, 21, and 28 after injection. After the 1st, 6th, and 12th injection, the maximum serum concentrations (Cmax) of MPA were observed on days 3.4 +/- 0.9, 4.3 +/- 2.2, and 3.7 +/- 2.6, respectively. Cmax of serum MPA during the 1st, 6th, and 12th treatment cycles were 3.75 +/- 1.27, 5.54 +/- 1.79, and 5.55 +/- 1.80 nmol/L, whereas the areas under the curve (AUC0-28 days) were 55.84 +/- 28.15, 95.45 +/- 26.56, and 98.81 +/- 21.84 nmol/L.day, respectively. There was significant interindividual variation in the pharmacokinetics of MPA after intramuscular injection of Cyclofem. No significant change was demonstrated in mean residence time (MRT) of MPA after single and multiple injection. There was a tendency of increase in Cmax and AUC0-28 days of MPA during the first 6 months of treatment, whereas no further enhancement was found between the 6th and 12th injection (p > 0.05). Peak levels of estradiol (E2) observed in Cyclofem users were within the normal range of the preovulatory phase. Results of this long-term study suggest that no drug accumulation occurred after repeated administration of Cyclofem in the Chinese women.
为提供关于含25mg醋酸甲羟孕酮（MPA）和5mg环丙孕酮的Cyclofem长期治疗安全性评估的药代动力学数据，在中国女性中研究了这种每月注射一次的避孕药单次和多次给药后MPA的药代动力学特征。9名健康育龄妇女按照每月一次的方案接受Cyclofem治疗，为期1年。在给药前以及注射后第1、3、5、7、14、21和28天采集血样。在第1次、第6次和第12次注射后，MPA的最大血清浓度（Cmax）分别在第3.4±0.9、4.3±2.2和3.7±2.6天观察到。第1次、第6次和第12次治疗周期中血清MPA的Cmax分别为3.75±1.27、5.54±1.79和5.55±1.80nmol/L，而曲线下面积（AUC0 - 28天）分别为55.84±28.15、95.45±26.56和98.81±21.84nmol/L·天。肌肉注射Cyclofem后，MPA的药代动力学存在显著的个体间差异。单次和多次注射后MPA的平均驻留时间（MRT）无显著变化。在治疗的前6个月中，MPA的Cmax和AUC0 - 28天有增加的趋势，而在第6次和第12次注射之间未发现进一步升高（p>0.05）。Cyclofem使用者中观察到的雌二醇（E2）峰值水平在排卵前期的正常范围内。这项长期研究结果表明，中国女性重复使用Cyclofem后未发生药物蓄积。
