药学学报, 2018, 53(10): 1721-1725
引用本文:
张娟红, 张军民, 王荣, 李文斌, 鹿辉, 孙月梅, 陈玉艳, 岳新瑞, 敏琼, 王昌, 赵安鹏, 贾正平. 肠道菌群介导的阿莫西林与硝苯地平相互作用研究[J]. 药学学报, 2018, 53(10): 1721-1725.
ZHANG Juan-hong, ZHANG Jun-min, WANG Rong, LI Wen-bin, LU Hui, SUN Yue-mei, CHEN Yu-yan, YUE Xin-rui, MIN Qiong, WANG Chang, ZHAO An-peng, JIA Zheng-ping. Interaction of amoxicillin and nifedipine mediated by intestinal flora[J]. Acta Pharmaceutica Sinica, 2018, 53(10): 1721-1725.

肠道菌群介导的阿莫西林与硝苯地平相互作用研究
张娟红1,2, 张军民2, 王荣1,2, 李文斌1, 鹿辉1, 孙月梅1, 陈玉艳1, 岳新瑞1,2, 敏琼1,2, 王昌1, 赵安鹏1, 贾正平1,2
1. 兰州总医院全军高原环境损伤防治重点实验室, 甘肃 兰州 730050;
2. 兰州大学药学院, 甘肃 兰州 730000
摘要:
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 8 μmol·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 4 μmol·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,AUC0-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。
关键词:    硝苯地平      阿莫西林      肠道菌群      生物利用度      疗效     
Interaction of amoxicillin and nifedipine mediated by intestinal flora
ZHANG Juan-hong1,2, ZHANG Jun-min2, WANG Rong1,2, LI Wen-bin1, LU Hui1, SUN Yue-mei1, CHEN Yu-yan1, YUE Xin-rui1,2, MIN Qiong1,2, WANG Chang1, ZHAO An-peng1, JIA Zheng-ping1,2
1. Key Laboratory for Prevention and Remediation of Plateau Environmental Damage, Lanzhou General Hospital, Lanzhou 730050, China;
2. School of Pharmacy, Lanzhou University, Lanzhou 730000, China
Abstract:
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 AUC0-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.
Key words:    nifedipine    amoxicillin    gut microbiota    bioavailability    curative effect   
收稿日期: 2018-05-18
DOI: 10.16438/j.0513-4870.2018-0463
基金项目: 国家自然科学基金资助项目(81673508).
通讯作者: 王荣,Tel:86-931-8994675,E-mail:wangrong-69@163.com;贾正平,Tel:86-931-8994652,E-mail:lzzyzhang@126.com
Email: wangrong-69@163.com;lzzyzhang@126.com
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参考文献:
[1] Koppel N, Rekdal VM, Balskus EP. Chemical transformation of xenobiotics by the human gut microbiota[J]. Science, 2017, 356:1246-1256.
[2] Wilson ID, Nicholson JK. Gut microbiome interactions with drug metabolism, efficacy, and toxicity[J]. Transl Res, 2017, 179:204-222.
[3] Carmody RN, Turnbaugh PJ. Host-microbial interactions in the metabolism of therapeutic and diet-derived xenobiotics[J]. J Clin Invest, 2014, 124:4173-4181.
[4] Alkhaja KA, Sequeira RP, Alkhaja AK, et al. Drug treatment of hypertension in pregnancy:a critical review of adult guideline recommendations[J]. J Hypertens, 2014, 32:454-463.
[5] Grigoriev A, Nikitina A, Yaroshenko I, et al. Development of a HPLC-MS/MS method for the simultaneous determination of nifedipine and lidocaine in human plasma[J]. J Pharm Biomed Anal, 2016, 131:13-19.
[6] Jia W, Xie G, Jia W. Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis[J]. Nat Rev Gastro Hepat, 2018, 15:111-128.
[7] Kim D. Gut microbiota-mediated drug-antibiotic interactions[J]. Drug Metab Dispos, 2015, 43:1581-1589.
[8] Yoo HH, Kim IS, Yoo DH, et al. Effects of orally administered antibiotics on the bioavailability of amlodipine:gut microbiota-mediated drug interaction[J]. J Hypertens, 2016, 34:156-162.
[9] Scott TA, Quintaneiro LM, Norvaisas P, et al. Host-microbe co-metabolism dictates cancer drug efficacy in C. elegans[J]. Cell, 2017, 169:442-456.
[10] Lin Z, Zu XP, Xie LS, et al. Research progress in mechanism of intestinal microorganisms in human diseases[J]. Acta Pharm Sin (药学学报), 2016, 51:843-852.
[11] Tang L, Fu LL, Shen LT, et al. Degradation of total saponins of Panax notoginseng by intestinal flora of rats in vitro[J]. Chin Tradit Herb Drugs (中草药), 2018, 49:396-400.
[12] Nicholson JK, Holmes E, Kinross J, et al. Host-gut microbiota metabolic interactions[J]. Science, 2012, 336:1262-1266.
[13] Kim I, Yoo D, Jung I, et al. Reduced metabolic activity of gut microbiota by antibiotics can potentiate the antithrombotic effect of aspirin[J]. Biochem Pharmacol, 2016, 122:72-79.
[14] Liu Q, Liu KX. Advances in enzymes and transporters-mediated pharmacokinetic mechanism for herb-drug interaction[J]. Acta Pharm Sin (药学学报), 2015, 50:406-412.
[15] Zhang JH, Chen YY, Sun YM et al. Plateau hypoxia attenuates the metabolic activity of intestinal flora to enhance the bioavailability of nifedipine[J]. Drug Deliv, 2018, 25:1175-1181.