左旋18-甲基炔诺酮经阴道给药的药代动力学和药效学研究

本文比较了左旋18-甲基炔诺酮(LNG)制剂Postinor单剂量(0.75mg)口服和阴道给药的药代动力学,并研究了这种制剂经阴道多次给药的药代动力学及对卵巢功能的影响。征集6例月经规则的健康育龄妇女。第一周期,每例对象每次于阴道深处放置一片Postinor,共8次,每2次间隔为48小时;第二周期,每例对象口服一片相同的LNG制剂,放免测定血清LNG、雌二醇和孕酮水平。结果表明在第一周期,除1例对象在中期有一较高的雌二醇峰以外,其余雌、孕激素水平均呈明显低平状态;口服和阴道放置相同的单剂量LNG以后血清LNG浓度时间曲线分别符合二室与一室开放模型。由此提示与口服相比,Postinor经阴道给药后吸收缓慢,且血清LNG峰值低,而消除过程则两种给药途径较为相似;Postinor经阴道给药可明显抑制排卵。

Pharmacokinetic and Pharmacodynamic Studies on Vaginally Administered Levonorgestrel

Comparative studies on pharmacokinetics of vaginally and orally administered levonor-gestrel(LNG)tablet(Postinor)in one single dose containing 0.75 mg LNG were perform-ed.The pharmacokinetics of LNG and its effects on ovarian functions were also studiedafter repeated vaginal administrations. Six women with regular menstruation and ovulation indicated by serum progesteronelevels during the luteal phase of the pretreatment cycle were recruited. During treatmentcycle 1,each woman was asked to insert one pill of LNG into the vagina deeply at about8:00 am every other morning from day 7 of the cycle for eight times.Blood samples weretaken immediately beforre and,1,2,4,8,12 and 24h after vaginal administration.Bloodsamples were taken at the same time every morning from day 9 to day 25 to assess serumLNG, E_2 and P levels by RIA. On day 7 of the 2 nd treatment cycle,one tablet of LNGwas ingested orally and blood samples were taken as mentioned during the first 48 h afterthe first vaginal administration of the drug in the treatment cycle 1.The serum LNGconcentration-time curves after vaginal and oral administration were found to be one-andtwo-compartment open model respectively,from which values for LNG pharmackineticparameters were calculated.The results suggest that absorption of LNG was much slowerand LNG peak levels were much lower after vaginal administration as compared with theoral intake.However,the elimination phase appeared similar with either way of administra-tion.Ovarian functions were depressed significantly and thus ovulation did not occur inall women as indicated by serum E_2 and P levels in the lst treatment cycle.