肠道菌群介导的阿莫西林与硝苯地平相互作用研究

Interaction of amoxicillin and nifedipine mediated by intestinal flora

采用染色法观察了给予阿莫西林后大鼠粪便样品中肠道菌群的变化。通过体外孵育实验结合LC-MS/MS检测法研究肠道菌群是否参与硝苯地平的代谢,以及给予阿莫西林后肠道菌群的改变对硝苯地平代谢的影响。结果发现给予阿莫西林后肠道菌群数量和种类减少。当孵育12 h后,硝苯地平组(N1)和阿莫西林+硝苯地平组(N2)中硝苯地平的剩余量分别为0.057 6和0.064 8μmol·L^(-1),而当孵育24 h后硝苯地平的剩余量分别为0.039 6和0.050 4μmol·L^(-1),结果表明肠道菌群参与了硝苯地平的代谢。此外,当给予阿莫西林后,硝苯地平的代谢减慢, AUC_(0-t)增加了39.10%, tmax提前了0.45 h, CL降低了34.71%,说明二者合用可能会增强硝苯地平的治疗效果。因此,抗生素与硝苯地平合用时,由肠道菌群介导的药物-药物相互作用不容忽视,是影响药物疗效的重要因素之一。

In this study, the change of intestinal microflora in rat fecal samples after amoxicillin administration was observed. In vitro incubation experiments combined with LC-MS/MS assay were used to test the role of intestinal flora in the metabolism of nifedipine. The effect of changes of intestinal flora was determined after amoxicillin administration on the metabolism of nifedipine. We found that the number and types of intestinal flora decreased after taking amoxicillin. After incubation for 12 h, the results showed that the remaining amounts of nifedipine in the N1 group（nifedipine） and N2 group（amoxicillin ＋ nifedipine） were 0.057 6 and 0.064 8 μmol·L^（-1）, respectively, while the remaining amounts of nifedipine after 24 h of incubation were 0.039 6 and 0.050 4 μmol·L^（-1）, respectively. These results show that the intestinal flora is involved in the metabolism of nifedipine. After administration of amoxicillin, the metabolism of nifedipine was slowed down, the AUC_（0-t）was increased by 39.10%, tmax was advanced by 0.45 h, and the CL was reduced 34.71%. The data suggest that the combination may enhance the therapeutic effect of nifedipine. Therefore, drug-drug interactions mediated by gut microbiota cannot be ignored when combined with antibiotics and nifedipine, one of the important factors affecting drug efficacy.