摘要
目的比较中国妇女单次及连续肌注cyclofem后血中醋酸甲羟孕酮(MPA)的药代动力学变化 ,为长期应用该长效避孕针的安全性提供依据。方法9名健康育龄妇女每月一次肌注cyclofem微晶水混悬剂(醋酸甲羟孕酮25mg+环戊丙酸雌二醇5mg) ,持续一年。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 ,采用自身对照比较此三个给药周期MPA的药代动力学特征。结果首次及第6、12次注射后 ,血中MPA分别于3.4±0.9、4.3±2 2及3 7±2.6天达峰浓度 ;MPA平均峰值血药水平(Cmax)为3.75±1.27、5.54±1.79及5.55±1.80nmol/L ;AUC0 -28 分别为55.84±28.15、95.45±26.56及98.81±21.84nmol/(L·d)。MPA的药代动力学存在明显的个体差异。三个给药周期MPA体内平均滞留时间(MRT)无显著变化 ,分别为11.98±1.08、12.77±0.47和12.43±0.64天。与首次注射后相比 ,第6个给药周期MPA的Cmax 和AUC0 -28显示有增高的倾向 ,但在其后6个月中 ,上述参数未见明显差别。
Aim Pharmacokinetic profiles of medroxyprogesterone acetate after single and multiple administration of cyclofem in Chinese women were analysed to provide pharmacokinetic data for safety evaluation on chronic treatment of this long_acting injectable contraceptive. Methods Nine healthy women received once_a_month injectable contraceptive cyclofem (aqueous microcrystalline suspension containing 25 mg medroxyprogesterone acetate and 5 mg cypionate )for up to 1 year. Blood samples were collected immediately prior to drug administration and to consecutive time points after injection. Intraindividual comparison was applied in this longitudinal study. Results After 1st, 6th and 12th injection, the maximum concentrations were observed on day 3.4±0.9, 4.3±2 2 and 3 7±2.6,reespectively. Cmax of 1st, 6th and 12th treatment cycles were 3.75±1.27,5.54±1.79 and 5.55±1.80 nmol/L,while AUC0-28 were 55.84±28.15,95.45±26.56 and 98.81±21.84 nmol/(L·d), respectively. There was significant interindividual variation in the pharmacokinetic profile of MPA after intramuscular injection of cyclofem. No meaningful change was observed in MRT. There was a tendency of increase in Cmax and AUC0-28 of MPA during first six months of treatment, whereas no statistically significant difference between 6th and 12th injection. Conclusion No obvious drug accumulation was occured after long-term use of cyclofem.
