白芍-甘草药对中异甘草素和甘草次酸在大鼠体内的药代动力学研究

Pharmacokinetics of Isoliquiritigenin and Glycyrrhetinic Acid of Baishao(Paeoniae Radix Alba)-Gancao(Glycyrrhizae Radix Et Rhizoma)in Rats

目的比较炙甘草与白芍配伍前后,炙甘草中异甘草素和甘草次酸的药代动力学行为差异。方法采用HPLC法同时测定大鼠灌服炙甘草药材、白芍-甘草药对后血浆中异甘草素和甘草次酸的含量,计算药代动力学参数并进行t检验。结果与灌胃给予异甘草素、甘草次酸单体相比,灌胃给予甘草药材和药对后达峰时间显著延迟,AUC增加,在体内的平均滞留时间延长。芍-甘药对3∶1和1∶1药动学无明显差异。与灌胃给予甘草药材相比,甘草次酸的Cnax,AUC两个比例中均有显著减小,而异甘草素的Cnax,AUC仅在1∶1比例中明显降低。结论白芍中物质可改变甘草中其他物质向异甘草素转化的速率,或促进异甘草素的代谢;同时抑制甘草酸、甘草次酸的吸收。

Objective To study the pharmacokinetic behavior of isoliquiritigenin and glycyrrhetinic acid of Baishao(Paeoniae Radix Alba)-Gancao(Glycyrrhizae Radix Et Rhizoma)in rats plasma and further understand the compatibility mechanism based on the theory of traditional Chinese medicine.Methods An HPLC method was developed for the simultaneous determination of isoliquiritigenin and glycyrrhetinic acid in rats plasma,and the validated method and T-test were applied to compare the pharmacokinetic parameters of isoliquiritigenin and glycyrrhetinic acid in rats after oral administration of pure chemical compounds,Gancao(Glycyrrhizae Radix Et Rhizoma)and Baishao(Paeoniae Radix Alba)-Gancao(Glycyrrhizae Radix Et Rhizoma).Results The pharmacokinetic comparison results of isoliquiritigenin and glycyrrhetinic acid showed that the peak time(Tmax)was significantly delayed,the area under concentration-time curve(AUC)was significantly increased and the average retention time(MRT)was prolonged after oral administration of Gancao(Glycyrrhizae Radix Et Rhizoma)and Baishao(Paeoniae Radix Alba)-Gancao(Glycyrrhizae Radix Et Rhizoma).Comparisons of pharmacokinetic parameters between oral Gancao(Glycyrrhizae Radix Et Rhizoma)and Baishao(Paeoniae Radix Alba)-Gancao(Glycyrrhizae Radix Et Rhizoma)showed that the t1/2 and Tmax of isoliquiritigenin were significantly prolonged,the Cmax and AUC of isoliquiritigenin and glycyrrhetinic acid were significantly decreased not only in the ratio of 3∶1 but also in the ratio of 1∶1,and the same results of isoliquiritigenin only turned up in the ratio of 1∶1.The pharmacokinetic parameters had no difference after oral administration of Baishao(Paeoniae Radix Alba)-Gancao(Glycyrrhizae Radix Et Rhizoma)between the ratio of 3∶1 and 1∶1.Conclusion The materials in Baishao(Paeoniae Radix Alba)can change the rate of transformation of other substances of Gancao(Glycyrrhizae Radix Et Rhizoma)to isoliquiritigenin or promote the metabolism of isoliquiritigenin,and at the same time,inhibit the absorption of glycyrrhetinic acid and glycyrrhetinic acid.