左旋18-甲基炔诺酮两种产品的药代动力学比较

A COMPARATIVE PHARMACOKINETIC STUDY ON TWO TYPES OF POSTCOITAL CONTRACEPTIVES CONTAINING LEVONORGESTREL

本文报告两种均含0.75mg左旋18-甲基炔诺酮(LNG)的事后片的药代动力学研究。每例对象服药后0～24小时的血清LNG浓度以放射免疫法进行测定;药—时曲线由微机以迭代法进行拟合,均符合二室开放模型。结果显示口服Postinor和国产片以后,血清LNG峰值,C_(max)分别为11.25±3.39(X±SD,下同)和5.89±1.72ng/ml(P<0.001);达峰时间T_(max)分别为1.9l±0.58 和3.08±1.24h,吸收半寿期T_(1/2a)分别是0.88±0.23和1.38±0.69h,服药后0～24h的药-时曲线下面积AUC_(0～24)分别为92.19±34.34和64.40±21.97ng/ml(P<0.05),两者亦均有明显差异。提示口服Postinor以后,LNG的吸收更迅速,更完全。然而服药后分布半寿期T_(1/2α)、消除半寿T_(1/2β)和总廓清率CL在统计学上无显著差异。故提示两种制剂经口服以后在体内的分布和消除过程较为相似。本文结果表明Postinor中LNG剂量可适当减少,而国产事后片若能改进制剂工艺,提高生物利用度也可适当减少剂量。

The pharmacokinetics of two types of postcoital contraceptives containing levonorges-trel (LNG) orally administered by ten healthy women of fertile age were reported. SerumLNG levels at different intervals from 0 through 24 h after administration were determinedby RIA. The LNG concentration-time curves of all the individuals in both groups fittedby iteration method were in agreement with a two-compartment model and LNG pharma-cokinetic analysis was carried out by self-made software. After oral intake of Postinor andChinese pill, the serum LNG peak, Cmax was 11.25±3. 39 and 5.89±1.72 ng/ml respec-tively, with very significant difference (p<0. 001); the time to C_(max), i. e. T_(max) was1.91±0.58 h and 3.08±1.24 h; T1/2a, 0.88±0.23 h and 1.38±0.69 h: AUCo～24,92.19±34.34 and 64.40±21.97 ng/ml/h respectively, also with significant difference too(p<0.05), suggesting that LNG absorption was faster and better after oral intake of Pos-tinor. However, LNG distribution and elimination processes were rather similar for bothagents, as their T1/2α, T1/2β and CL did not show significant difference (p>0. 05).The results of the study suggested that the dose of LNG (0.75mg) in Postinor seemed tobe excessive for effective contraception while that of the Chinese pill would also be redu-ced in case the bioactivity will be increased.