Heikinheimo O, Ylikorkala O, Turpeinen U, Lähteenmäki P
Department of Medical Chemistry, University of Helsinki, Finland.
Acta Endocrinol (Copenh). 1990 Sep;123(3):298-304. doi: 10.1530/acta.0.1230298.
The pharmacokinetics and metabolism of RU 486 were characterized in 17 women who received a single dose of 600 mg of RU 486 for termination of an early unwanted pregnancy. Based on the clinical outcome and serum chorionic gonadotropin values, the subjects were divided into two groups: those who aborted completely (i.e. responders: N = 13) and those who did not respond to RU 486 treatment (i.e. non-responders: N = 4). The serum levels of RU 486, the monodemethylated, didemethylated and hydroxylated metabolites of RU 486 were measured by HPLC preceded by column chromatography. There were no significant differences in the serum levels of RU 486 or its metabolites between the two groups. The serum concentrations of alpha 1-acid glycoprotein, the binding protein for RU 486, were quantitated by immunoturbidimetry. The alpha 1-acid glycoprotein concentrations were similar in responders and non-responders. The metabolism of RU 486 was also studied by fractionating extracts of serum pools of responders and non-responders on thin-layer chromatography, and subsequent RIA analysis of the eluates of the sliced thin-layer chromatography. Spots with similar distribution and percentages of cross-reactivity were found in both groups on the chromatography; the results were also similar to those from a serum pool to which synthetic RU 486 and its three metabolites had been added. Hence it is concluded that failure to abort in response to RU 486 therapy is not associated with altered pharmacokinetics or metabolism of RU 486.
对17名接受600毫克米非司酮单次给药以终止早期意外妊娠的女性进行了米非司酮的药代动力学和代谢特征研究。根据临床结局和血清绒毛膜促性腺激素值，将受试者分为两组：完全流产者（即反应者：N = 13）和对米非司酮治疗无反应者（即无反应者：N = 4）。在柱色谱法预处理后，通过高效液相色谱法测定血清中米非司酮、米非司酮的单去甲基、双去甲基和羟基化代谢产物的水平。两组之间米非司酮及其代谢产物的血清水平无显著差异。通过免疫比浊法对米非司酮的结合蛋白α1-酸性糖蛋白的血清浓度进行定量。反应者和无反应者的α1-酸性糖蛋白浓度相似。还通过对反应者和无反应者血清池提取物进行薄层色谱分离，并对薄层色谱切片洗脱液进行后续放射免疫分析，研究了米非司酮的代谢情况。两组在色谱图上均发现了具有相似分布和交叉反应百分比的斑点；结果也与添加了合成米非司酮及其三种代谢产物的血清池的结果相似。因此得出结论，米非司酮治疗后未能流产与米非司酮药代动力学或代谢改变无关。
