赛米司酮或米非司酮经口给药终止猕猴早孕有效剂量的研究

目的:观察赛米司酮终止猕猴早孕的效果及对阴道出血量的影响,为新药研发提供实验依据。方法:妊娠猕猴随机分为7组,其中受试药赛米司酮和阳性对照药米非司酮均分为低、中、高剂量3个组(5 mg/kg.d、10 mg/kg.d和15mg/kg.d);另设一赋型剂组(0.5%羧甲基纤维素钠),每组动物各5只。于月经周期第42～48天,空腹状态下分别给予不同剂量的赛米司酮或米非司酮,1次/日,连续3天,第4天再加用米索前列醇200μg,观察用药后的不良反应,并于第15天经B超判断孕猴流产及胚胎发育状况。结果:赛米司酮高剂量组完全流产率为60.00%(3/5),中剂量组为20.00%(1/5),而低剂量组未见流产;阳性对照组米非司酮在相应剂量下完全流产率分别为80.00%(4/5)、40.00%(2/5)和20.00%(1/5)。赛米司酮组和米非司酮组总的流产率分别为26.67%(4/15)和46.67%(7/15),两组间的差异无统计学意义(P>0.05)。赛米司酮组阴道持续出血时间明显短于米非司酮组,出血量明显少于米非司酮组(P<0.05)。结论:赛米司酮能有效终止猕猴早孕,且能明显地缩短出血时间和减少出血量。

Study on the effective doses of samistone and mifepristone in terminating early pregnancy of rhesus monkeys by oral administration

Objective:To observe the effect of samistone on terminating early pregnancy of rhesus monkeys and its impact on the amount of vaginal bleeding,provide an experimental basis for researching and developing new drugs. Methods:The pregnant rhesus monkeys were randomly divided into seven groups: the rhesus monkeys in samistone group and mifepristone group were divided into low-dose group,middle-dose group,and high-dose group(5 mg·kg-1·d-1,10 mg·kg-1·d-1,and 15 mg·kg-1·d-1),respectively;excipient(0.5% sodium carboxymethylcellulose) group was designed,five rhesus monkeys in each group.The rhesus monkeys in samistone group and mifepristone group were treated with different doses of samistone and mifepristone in a fasting state on the 42nd-48th day during menstrual cycle,once a day for three days,200 μg misoprostol was administrated on the fourth day;the adverse reactions were observed after treatment,B ultrasound was applied to predict abortion and development of embryos on the fifteenth day. Results:The complete abortion rates in high-dose samistone group and middle-dose samistone group were 60.00%(3/5) and 20.00%(1/5),respectively;while in low-dose samistone group,no abortion occurred.The complete abortion rates in high-dose mifepristone group,middle-dose mifepristone group,and low-dose mifepristone group were 80.00%(4/5),40.00%(2/5),and 20.00%(1/5),respectively.The total abortion rates in samistone group and mifepristone group were 26.67%(4/15) and 46.67%(7/15),there was no statistically significant difference between the two groups(P>0.05).The duration time of vaginal bleeding in samistone group was significantly shorter than that in mifepristone group,the amount of vaginal bleeding in samistone group was significantly less than that in mifepristone group(P<0.05). Conclusion:Samistone can terminate early pregnancy of rhesus monkeys,shorten the bleeding time,and reduce the amount of vaginal bleeding obviously.