大白鼠皮下植入米非司酮埋植剂血药浓度和抑制异位子宫内膜效果的观察

目的观察大鼠皮下植入米非司酮埋植剂后的血药浓度变化及抑制大鼠子宫内膜异位症的效果。方法取体质量170～190g Wister雌性正常大鼠，分别在正常大鼠和动物模型大鼠（实验组5组和对照组）皮下埋植单根0．75cm、1．5cm、3．0cm和2根、3根3cm长米非司酮埋植剂（外径2．5mm），对照组植入2根3．0cm不含药的埋植剂。正常大鼠给药1个月．定期取血用HPLC法测血药浓度。动物模型大鼠给药3个月．用MRI测定异位子宫内膜体积并计算抑制率。结果不同剂量的米非司酮皮下埋植剂皆在植入体内7d时，血药浓度达到最高：随着给药剂量加大，血药浓度峰值也趋向增高，但7d后血药浓度逐渐下降，14d后除3根剂量组的血药浓度显著较高外（约0．18～0．20μg／ml），其他较低剂量组之间的血药浓度差异无统计学意义（约0．10～0．13μg/ml）。大鼠皮下植入埋植剂的剂量与血药浓度峰值呈线性关系。动物模型皮下植入1根1．5cm、3．0cm或2根3．0cm长埋植剂1个月时，异位内膜抑制率分别为18．6％±17．3％、31．5％±12．7％、72．2％±12．3％，与对照组比较差异有统计学意义，并且不再随剂量加大而显著提高抑制效果。结论 米非司酮皮下埋植剂作为治疗子宫内膜异位症的长效制剂是可行的．

Serum mifepristone level and effect of mifepristone-releasing implants on the endometriosis in rats

Objective To observe the serum mifepristone levels and the inhibitory effect of mifepristone-releasing implants on the endometriosis in rats. Methods The normal rats and the rats with endometriosls were subdermally implanted a piece of the 0.75,1.5,3.0 cm, 2 or 3 pieces of 3.0 cm lenth of mifepristone-releasing implants resepectively. The serum levels of mlfepristone in normal rats were determined by HPLC. The changes of volumes of explants in rat with endometriosis were measured by MRI at 1,2,3 months after administration. Results The peak concentrations of mifepristone found in all normal rats at the 7th days and increased in proportion to dose. After 7 days, the serum levels of mifepristone decreased gradually. After administration 14 days, the concentrations of serum mifepristone in all normal rats （about 0.10～ 0.13 μg/ml） showed no significant differences with rats implanted 3 pieces of 3.0 cm lenth of mifepristone-releasing implants （about 0.18 ～ 0.20 μg/ml）.Administration of 1/2,1,2 pieces of 3.0 cm lenth of mifepristone-releasing implants resulted in inhibitory rates of 18.6 % ± 17.3 %, 31.5 % ± 12.7 % and 72.2 % ± 12.3 % respectively at 1 month. But administration of 3 pieces 3.0 cm lenth of implants,better inhibitory effects were not observed. Conclusion It is demonstrated that subcutaneous administrating mifepristone-releasing implant shows obvious therapautical effect on endometriosis.