抗菌剂合用对芍药甘草汤中甘草酸生物利用度的降低作用及减少该作用的方法Ⅲ:芍药甘草汤连续给药的回复作用

Reduction of Bioavailability of Glycyrrhizin Fim Shaoyao-Gancao-Tang by Co-administered Antibacterial Drugs and Ways of Minimizing it (Part Ⅲ) Restorative Effects of Repeated Administration of Shaoyao-Gancao-Tang

关键词:  药物相互作用  芍药甘草汤  西药  甘草酸  药动学  肠内细菌  代谢活性

Key words:  drug-drug interaction  Shaoyao-Gancao-Tang  antibacterial druns  glycyrrhizin  pharmacokinetics  intestinal bacteria

摘要:

在本研究的第Ⅱ部分,已经报告了和芍药甘草汤(SGT)合用的抗菌剂组合AMPC-MET(amoxicillin,AMPC,and metronidazole,MET)显著降低了SGT中甘草酸 (glycyrrhizin,GL)的生物利用度,原因在于其降低了肠内细菌将GL代谢成甘草次酸 (18β glycyrrheticacid,GA)的活性。在本文,即本研究的第Ⅲ部分,笔者对AMPC-MET的降低作用的持续时间以及可减少这种作用的适当的合并给药方案进行了探讨。实验结果显示,肠内细菌的GL代谢活性被AMPC-MET降低后,需要 12d才可恢复到正常水平,而AMPC-MET给药 1d后开始进行SGT给药,被AMPC-MET显著降低了的肠内细菌的GL代谢活性以及GA血药浓度4d后得以快速恢复到正常水平。本研究的结果表明,在抗菌剂和SGT的合并疗法中,为了减少抗菌剂对SGT中GL生物利用度的影响,可在抗菌剂给药1d或2d后对SGT进行连续投药。该给药方案也可应用于临床上。

Abstract:

(part Ⅲ):In part Ⅱ, we reported that the co-administration of antibacterial drugs AMPC-MET (amoxicillin, AMPC,and metronidazole, MET) significantly decreased the bioavailability of glycyrrhizin (GL) fim Shaoyao-Gancao-Tang (SGT),due to their decreasing effects on the Gl-metabolizing activity of intestinal bacteria. In this part Ⅲ, the lasting time period of the influences of AMPC-MET on the GL-metabolizing activity and an appropriate medication regiment to minimize the influences were investigated. The results showed that the decreasing effects of AMPC-MET on the GL-metabolizing activity lasted for approx 12 days. However, repetitive administration of SGT starting 1 day after the treatment with AMPC-MET for 4 days significantly accelerated the recovery of the reduced plasma 18 β-glycyrrhetic acid (GA) concentration and the GL-metabolizing activity of rat feces. The present results suggest that it may be clinically useful to administer SGT repetitively starting 1 or 2 days after the antibiotic treatment during combination therapy with SGT and antibiotics to accelerate the recovery of the reduced bioavailability of GL in SGT.