国产半合成米非司酮临床药代动力学

Pharmacokinetics of Chinese-made Mifepristone (RU486)and Its Metabolites in Pregnant Women Orally Administered with Various Doses

２４例早孕妇女分别口服不同剂量的国产半合成米非司酮（ＲＵ４８６），以ＨＰＬＣ测定其血清母药及其代谢产物（ＲＵ４２６３３，ＲＵ４２８４８和ＲＵ４２６９８）浓度，并以免疫火箭电泳测定α－酸糖蛋白（ＡＡＧ）血清水平。结果显示米非司酮吸收和代谢均很迅速，口服２０ｍｉｎ后可测得母药．２ｈ以后ＲＵ４２６３３水平开始超过母药水平。母药峰浓度（ＣＭＡＸ）与剂量不成比例。按二室开放模型和非空模型计算，母药消除半衰期均随剂量而变化。但在６００ｍｇ组，ＣＭＡＸ与０、２４和４８ｈ的ＡＡＧ平均水平呈显著正相关（ｒ＝０．９２９９，Ｐ＜０．０１），结果提示米非司酮在人体内代谢里非线性过程，ＡＡＧ在一定程度上影响该化合物血清浓度与代谢过程。

Serum concentrations of mifepristone (RU486 ) and its metabolites (RU42633 \ RU42848.RU42698) were determined by HPLC. and serum levels of α1-acid glycoprotein (AAG) by immunoelectrophoresis in 24 pregnant women orally administered with various doses of Chinese-made RU486. The results showed that absorption and biotransformation of RU486 were fast as indicated by the fact that the parent compound could be measured in serum 20 min after intake and serum levels of RU42633 were biger than those of RU486 from 2h. Serum RU486 peak levels (Cmax)were not in proportion to the doses, with which however, the half-life of elimination (T1/2) varied, according to the two-compartment open model and non-compartment model.There was a significant positive correlation (r=0. 93, P<0. 01 ) between the individual RU486 Cmaxand the mean AAG levels 0. 24.48h after administration of 600 mg. The results suggest that metabolism of RU486 is a non-linear kinetic process,which is influenced by serum AAG levels in some degree.