孕妇及非孕妇口服不同剂量RU 486后的药物动力学研究

非孕妇(n=9)及早孕妇(n=36)口服不同剂量RU 486后,以HPLC测定服药后RU486及其代谢产物RU 42633、RU 42848和RU 42698的血浆浓度,结果显示不论妊娠与否,药物的吸收及代谢都很迅速;服药后20 min 即可测得血浆中的RU 486及其代谢产物;母药达峰时间Tmax 均为1～2h,其峰浓度Cmax 对数与剂量对数之间呈显著正相关。服相同剂量后,非孕组药-时曲线水平及药时曲线下面积AUC 大于早孕组,但两组间并无显著性差异(P>0.05)。无论非孕组及早孕组,口服25 mg、100 mg 和200 mg后,RU 486代谢符合二室开放模型,口服400 mg 和600mg 后则呈非线性动力学过程。

Pharmacokinetic Study on RU 486 and Its Metabolites After Oral Administration of Various Doses in Pregnant and.Non-pregnant Women

Plasma levels of RU 486 and its metabolites, RU 42633, RU 42643, and RU 42698 were determined by HPLC in nonpregnant (n = 9) and early pregnant (n = 36) women orally administered with different doses of RU 486. The results showed that absorption and initiation of metabolism of RU 486 were rapid in both groups, as indicated by the fact that RU 486 and its 3 metabolites could be measured in plasma 20 minutes after administration and that Tmax of RU 486 was between 1 and 2 hours. There was a positive correlation (p 0.01) between the logarithm of Cmax and that of the corresponding doses orally administered in each group. The plasma drug-time curve of each dose in the nonpregnant group was higher than that in the pregnant group, and so was the AUC. However, there was no significant difference in these 2 parameters between the 2 groups (p 0.05). Metabolism of Ru 486 was in agreement with 2-compartment open models after oral administration of 25 mg, 100 mg, and 200 mg, and presented as a process of nonlinear kinetics after the intake of 400 mg and 600 mg in both pregnant and nonpregnant women. (author's modified)