米索前列醇片不同给药途径的人体药动学研究

Pharmacokinetic Studies of Misoprostol Tablet Following Oral,Sublingual and Vaginal Administration in Female Volunteers

目的比较米索前列醇不同给药途径(口服、舌下和阴道)药动学特征。方法采用平行试验设计,30名中国健康女性志愿受试者随机分为3组,分别空腹口服、舌下含服和阴道给予400μg米索前列醇片,采用液相色谱-串联质谱法测定受试者血浆中米索前列醇活性代谢物米索前列酸的浓度。结果受试者空腹口服、舌下含服和阴道给药后的主要药动学参数:tm ax分别为(0.18±0.05),(0.40±0.14)和(5.05±1.80)h,mρax分别为(1 424±380),(783±285)和(302±198)ng.L-1,t1/2分别为(0.61±0.32),(0.82±0.18)和(5.27±4.38)h,AUC0-t分别为(698±138),(824±302)和(1 313±691)ng.h.L-1,AUC0-∞分别为(709±143),(846±306)和(1 816±727)ng.h.L-1。结论米索前列醇片经不同途径给药后的药动学有较大差异。空腹口服给药后吸收迅速,米索前列酸达峰最快,舌下含服给药tm ax略有延长,阴道给药tm ax明显滞后。达峰浓度以空腹口服给药最高,舌下含服次之,阴道给药最低。与空腹口服和舌下含服相比,阴道给药AUC最高,但个体差异较大。

OBJECTIVE To compare the pharmacokinetic profiles of orally,sublingually,and vaginally administered misoprostol tablets in Chinese healthy female volunteers.METHODS A total of 30 women were randomized to receive 400 μg of misoprostol by one of three routes：（i） oral（ii） sublingual（iii） vaginal.The major active metabolite of misoprostol acid was determined in plasma using a liquid chromatographic-tandem mass spectrometric method.RESULTS The main pharmacokinetic parameters of misoprostol acid administered by oral,sublingual and vaginal routes were as follows：tmax（0.18±0.05）,（0.40±0.14） and（5.05±1.80） h,ρmax（1 424±380）,（783±285） and（302±198） ng·L-1,t1/2（0.61±0.32）,（0.82±0.18） and（5.27±4.38） h,AUC0-t（698±138）,（824±302） and（1 313±691） ng·h·L-1,AUC0-∞（709±143）,（846±306） and（1 816±727） ng·h·L-1,respectively.CONCLUSION There are significant differences in the pharmacokinetics of misoprostol administered by oral,vaginal and sublingual routes.Oral misoprostol had a higher peak plasma concentration of misoprostol acid and a shorter duration to maximum concentration than either sublingual or vaginal misoprostol.ρmax obtained after vaginal administration is the lowest,but the AUC is significantly higher than those in the oral and sublingual groups.However,there was a wide individual variability in the vaginal group.