The influence of broad-spectrum antibiotics on the pharmacokinetics and biotransformation of major constituents of Shaoyao-Gancao decoction (SGD) in rats was investigated. The pharmacokinetic behaviors of paeoniflorin (PF), albiflorin (AF), liquiritin (LT), isoliquiritin (ILT), liquiritin apioside (LA), isoliquiritin apioside (ILA), and glycyrrhizic acid (GL), seven major constituents of SGD, as well as glycyrrhetinic acid (GA), a major metabolite of GL, were analyzed. A 1-week pretreatment with broad-spectrum antibiotics (ampicillin, metronidazole, neomycin, 1 g L-1; and vancomycin, 0.5 g L-1) via drinking water reduced plasma exposure of the major constituents. The AUC0-24 h of PF and LT was significantly decreased by 28.7% and 33.8% (P < 0.05 and P < 0.005), respectively. Although the differences were not statistically significant, the AUC0-24 h of AF, ILT, LA, ILA, and GL was decreased by 31.4%, 50.9%, 16.9%, 44.1%, and 37.0%, respectively, compared with the control group. In addition, the plasma GA exposure in the antibiotic-pretreated group was significantly lower (P < 0.005) than the control group. The in vitro stability of the major constituents of SGD in the rat intestinal contents with or without broad-spectrum antibiotics was also investigated. The major constituents were comparatively stable in the rat duodenum contents, and the biotransformation of GL mainly occurred in the rat colon contents. In summary, broad-spectrum antibiotics suppressed the absorption of the major constituents of SGD and significantly inhibited the biotransformation of GL to GA by suppressing the colon microbiota. The results indicated a potential clinical drug-drug interaction (DDI) when SGD was administered with broad-spectrum antibiotics.

中文翻译：

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口服广谱抗生素预处理可改变少药甘草汤主要成分的药代动力学。

研究了广谱抗生素对少药甘草汤（SGD）主要成分的药代动力学和生物转化的影响。SGD的七种主要成分pa药花粉素（PF），白花素（AF），脂蛋白（LT），异脂蛋白（ILT），脂蛋白apioside（LA），异脂蛋白芦荟苷（ILA）和甘草酸（GL）的药代动力学行为以及GL的主要代谢产物甘草次酸（GA）进行了分析。通过饮用水对广谱抗生素（氨苄青霉素，甲硝唑，新霉素，1 g L-1和万古霉素，0.5 g L-1）进行为期1周的预处理，可减少主要成分的血浆暴露。PF和LT的AUC0-24 h分别显着降低了28.7％和33.8％（P <0.05和P <0.005）。尽管差异没有统计学意义，与对照组相比，AF，ILT，LA，ILA和GL的AUC0-24 h分别降低了31.4％，50.9％，16.9％，44.1％和37.0％。此外，抗生素预处理组的血浆GA暴露显着低于对照组（P <0.005）。还研究了在有或没有广谱抗生素的情况下，大鼠肠内容物中SGD主要成分的体外稳定性。主要成分在大鼠十二指肠内相对稳定，而GL的生物转化主要发生在大鼠结肠内。总之，广谱抗生素通过抑制结肠菌群，抑制了SGD主要成分的吸收，并显着抑制了GL向GA的生物转化。