Heikinheimo O
Department of Medical Chemistry, University of Helsinki, Finland.
J Steroid Biochem. 1989 Jan;32(1A):21-5. doi: 10.1016/0022-4731(89)90008-3.
Serum levels of RU 486 were measured by high performance liquid chromatography (HPLC) following oral intake of 12.5, 25, 50 and 100 mg twice daily (b.i.d.) for 4 days, 50 mg b.i.d. for 7 days, as well as a single dose of 200 mg of RU 486. The pharmacokinetics of RU 486 were not linear: when the daily dose of RU 486 was 100 mg or more, the serum levels were similar. The pharmacokinetic behaviour of RU 486 during the treatment period was similar between the study subjects, whereas the elimination phase pharmacokinetics showed wide individual variation. Also the mean elimination phase half-lifes (t 12) of RU 486 varied from 25.5 to 47.8 h in the groups of different regimen, yet the variation between different groups was not statistically significant. The areas under the concentration curves (AUC) were calculated. In the multiple dose study (mds) the AUC0----12h:s decreased when the administered dose of RU 486 was increased. The AUC0----12h seen after administration of 100 mg b.i.d. x 4d. (mean +/- SEM = 0.43 +/- 0.04 mumol/l x h/mg) was significantly (P less than 0.05) lower than the AUC0----12h:s obtained with administration of 12.5 mg b.i.d. x 4d. (1.49 +/- 0.37 mumol/l x h/mg), 25 mg b.i.d. x 4d. (1.09 +/- 0.15 mumol/l x h/mg), and 50 mg b.i.d. x 7d. (0.72 +/- 0.11 mumol/l x h/mg). The AUC0----infinity obtained by administration of a single dose of 200 mg of RU 486 (sds) was 0.67 +/- 0.21 mumol/l x h/mg. It is concluded that if multiple dose administration of RU 486 is preferred, daily administration of relatively small doses of RU 486 over several days seem to be advantageous.
在每日两次口服12.5毫克、25毫克、50毫克和100毫克，共4天；每日两次口服50毫克，共7天；以及单次口服200毫克米非司酮（RU 486）后，采用高效液相色谱法（HPLC）测定血清中RU 486的水平。RU 486的药代动力学并非呈线性：当RU 486的日剂量为100毫克或更高时，血清水平相似。在治疗期间，研究对象之间RU 486的药代动力学行为相似，而消除相药代动力学显示出较大的个体差异。此外，不同给药方案组中RU 486的平均消除相半衰期（t1/2）在25.5至47.8小时之间变化，但不同组之间的差异无统计学意义。计算了浓度曲线下面积（AUC）。在多剂量研究（mds）中，当RU 486的给药剂量增加时，AUC0→12h:s降低。每日两次口服100毫克×4天（均值±标准误=0.43±0.04微摩尔/升×小时/毫克）后观察到的AUC0→12h显著低于（P<0.05）每日两次口服12.5毫克×4天（1.49±0.37微摩尔/升×小时/毫克）、每日两次口服25毫克×4天（1.09±0.15微摩尔/升×小时/毫克）和每日两次口服50毫克×7天（0.72±0.11微摩尔/升×小时/毫克）所获得的AUC0→12h:s。单次口服200毫克RU 486（sds）所获得的AUC0→∞为0.67±0.21微摩尔/升×小时/毫克。结论是，如果首选RU 486的多剂量给药，那么在几天内每日给予相对小剂量的RU 486似乎是有利的。
