Kekkonen R, Heikinheimo O, Mandelin E, Lähteenmäki P
Department of Medical Chemistry, University of Helsinki, Finland.
Contraception. 1996 Oct;54(4):229-34. doi: 10.1016/s0010-7824(96)00193-x.
Relatively low doses of the antiprogestin mifepristone (RU 486) have recently proven to be efficient for a variety of possible clinical uses of the drug. However, the pharmacokinetics after low single oral doses have not been characterized. We evaluated the pharmacokinetics of mifepristone following single ingestion of 2 and 25 mg in five women as well as repeated ingestion of 8 mg in two women. Maximal serum concentrations were reached rapidly (within 0.5-2 h) with all doses used. Serum mifepristone concentrations were proportional to the oral doses taken. The mean (+/- SD) areas under the concentration curves (AUCs) (0-24 h) were 1134 (+/- 144), 4846 (+/- 64), and 17,015 (+/- 4,421) h x ng/mL following 2, 8, and 25 mg doses, respectively. No cumulative increases in serum concentrations were detected with prolonged daily administration of 8 mg of mifepristone. The study subjects appeared to vary in their ability to metabolize mifepristone, as two different half-lives (t1/2) emerged after both 2 and 25 mg single doses (24.2 +/- 0.6 [SD] h for three subjects; and 44.4 +/- 1.8 [SD] h for two subjects). We conclude that within the dose range of 2-25 mg/day, the pharmacokinetics of mifepristone are linear, unlike those seen following ingestion of higher daily doses. Keeping in mind previously published data on the biological effects of low dose mifepristone administration, these data infer that certain effects of the drug, such as inhibition of ovulation, might be achieved at serum concentrations of approximately 100 ng/mL.
近期研究表明，相对低剂量的抗孕激素米非司酮（RU 486）在多种可能的临床应用中具有显著疗效。然而，单次口服低剂量米非司酮后的药代动力学特征尚未明确。我们评估了5名女性单次服用2mg和25mg米非司酮以及2名女性重复服用8mg米非司酮后的药代动力学情况。所有使用剂量均能迅速达到血清最大浓度（0.5 - 2小时内）。血清米非司酮浓度与口服剂量成正比。2mg、8mg和25mg剂量后的平均（±标准差）浓度曲线下面积（AUCs）（0 - 24小时）分别为1134（±144）、4846（±64）和17015（±4421）h x ng/mL。每日持续服用8mg米非司酮未检测到血清浓度的累积增加。研究对象在米非司酮代谢能力上存在差异，单次服用2mg和25mg后出现了两种不同的半衰期（t1/2）（3名受试者为24.2±0.6[标准差]小时；2名受试者为44.4±1.8[标准差]小时）。我们得出结论，在2 - 25mg/天的剂量范围内，米非司酮的药代动力学呈线性，这与高剂量每日服用后的情况不同。结合先前发表的关于低剂量米非司酮生物学效应的数据，这些数据表明，该药物的某些效应，如抑制排卵，可能在血清浓度约为100ng/mL时实现。
