肠道菌群调控对药动学特征的影响

常瑞蕊, 陈卫东, 周婷婷

中国药学杂志 ›› 2019, Vol. 54 ›› Issue (15) : 1211-1215.

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中国药学杂志 ›› 2019, Vol. 54 ›› Issue (15) : 1211-1215. DOI: 10.11669/cpj.2019.15.002
综述

肠道菌群调控对药动学特征的影响

  • 常瑞蕊1,2, 陈卫东2*, 周婷婷1,2*
作者信息 +

Influence of Gut Microbiota Regulation on Pharmacokinetic Characteristics

  • CHANG Rui-rui1,2, CHEN Wei-dong2*, ZHOU Ting-ting1,2*
Author information +
文章历史 +

摘要

肠道是口服药物代谢的重要场所,肠道中寄居着大量的肠道菌群,这些肠道菌群数量大,种类多,在肠道中起着重要的作用,同时也被认为是参与口服药物代谢的重要“器官”。肠道菌群在正常状态下维持着动态平衡,然而,当一些外部条件或机体自身状态发生改变时,肠道菌群的动态平衡被打破,药物在体内的代谢就会受到影响,其药动学特征也会发生相应的变化。笔者综述了由于代谢紊乱、内分泌失调以及精神异常引起的病理变化,种族和年龄的不同导致的生理差异以及传统中药复方和抗生素益生菌在当今临床上联合用药的影响下,引起肠道菌群发生的相应变化,以及药物在肠道中代谢的改变,从而导致药物药动学特征产生了影响的研究。笔者不仅通过肠道菌将病理生理状态以及联合用药与药动学联系起来,更为后续进一步研究肠道菌群调控对药物在生物体内药动学特征的影响提供参考。

Abstract

Intestinal tract plays an important role in the oral drug metabolism, and the gut microbiota which are huge amount and great variety is regard as a vital organs during drug metabolism. The gut micrbiota keep the balance normally, unless some external factors and biological factors change. The changed metabolism of drug would influence the pharmacokinetic characteristics of it. The relevant literatures in recent years about the influence of gut microbiota regulation on pharmacokinetics have been collected in this review, in order to summarize the current research method of pharmacokinetics by gut microbiota and influence of gut microbiota regulation on pharmacokinetics caused by pathologically induced by metabolic disorders, endocrine dyscrasia and insanity, physiology induced by the difference in race and age and drug combination like Chinese traditional medicine, antibiotics and probiotics. This paper not only makes the combination of pathophysiological state and pharmacokinetic characteristics by gut microbiota, but also provides a reference for further research about the influence of gut microbiota regulation on pharmacokinetic characteristics.

关键词

肠道菌群 / 药动学 / 菌群调控 / 生物转化

Key words

gut microbiota / pharmacokinetics / flora regulation / biotransformation

引用本文

导出引用
常瑞蕊, 陈卫东, 周婷婷. 肠道菌群调控对药动学特征的影响[J]. 中国药学杂志, 2019, 54(15): 1211-1215 https://doi.org/10.11669/cpj.2019.15.002
CHANG Rui-rui, CHEN Wei-dong, ZHOU Ting-ting. Influence of Gut Microbiota Regulation on Pharmacokinetic Characteristics[J]. Chinese Pharmaceutical Journal, 2019, 54(15): 1211-1215 https://doi.org/10.11669/cpj.2019.15.002
中图分类号: R969.1   

参考文献

[1] SCALDAFERRI F, GERARDI V, LOPETUSO L R, et al. Gut microbial flora, prebiotics, and probiotics in IBD: their current usage and utility[J] . Biomed Res Inter, 2013, 2013: 1-9.
[2] D′ARGENIO V, SALVATORE F. The role of the gut microbiome in the healthy adult status[J] . Clin Chim Acta, 2015, 451(2014):97-102.
[3] GENG D, FANG M Y, LI D L, et al. Research progress in terms of interaction between Chinese medicine components and intestinal microenvironment[J] . Sci Sin Vitae(中国科学:生命科学), 2018, 48(4):379-389.
[4] LI Q R, HAN Y, DU J B, et al. Advances in the study of intestinal flora and neuropsychiatric diseases[J] . Prog Physiol Sci(生理科学进展), 2016, 47(5):365-368.
[5] LIU C X. Gut microbiota: the effects of health, illness and medicines[J] . Chin J Antib Chin J Antibio(中国抗生素杂志), 2018, 43(1):1-14.
[6] HUANG K, WU L L, YANG Y S. Research progress of the relationships between gastrointestinal microbiota and human diseases[J] . Infect Dis Inf(传染病信息), 2017, 30(3):133-137.
[7] NOH K, KANG Y R, NEPAL M R, et al. Impact of gut microbiota on drug metabolism: an update for safe and effective use of drugs[J] . Arch Pharm Res, 2017, 40(12):1345-1355.
[8] ZHANG W T, HUANG Q W, XIANG Z M, et al. Biotansformation of polydatin by rat intestinal bacteria[J] . Chin Pharm J(中国药学杂志), 2012, 47(8):631-633.
[9] YAO Y, MA X, LI T, et al. Quantification of isoflavone glycosides and aglycones in rat plasma by LC-MS/MS: troubleshooting of interference from food and its application to pharmacokinetic study of Semen Sojae Praeparatum extract[J] . J Pharm Biomed Anal, 2018, 161: 444-454.
[10] LIU J, CHANG R, ZHANG X, et al. Non-isoflavones diet incurred metabolic modifications induced by constipation in rats via targeting gut microbiota[J] . Front Microb, 2018, 9: 1-11.
[11] XU J, ZHAO M, QIAN D, et al. Comparative metabolism of Radix scutellariae extract by intestinal bacteria from normal and type 2 diabetic mice in vitro[J] . J Ethnopharm, 2014, 153(2):368-374.
[12] MOHAMADKHANI A. On the potential role of intestinal microbial community in hepatocarcinogenesis in chronic hepatitis B[J] . Cancer Med, 2018, 7(7):3095-3100.
[13] INOUE T, NAKAYAMA J, MORIYA K, et al. Gut dysbiosis associated with hepatitis C virus infection[J] . Clin Infect Dis, 2018,DOI:10.1093/cid/ciy205.
[14] GAO C, SHAN C, SU R X, et al. Metabolic differences of glycyrrhizin in the intestinal flora of patients with hepatitis and liver cancer[J] . Chin Tradit Pat Med (中成药), 2017, 39(2):393-398.
[15] RYAN C, HYEMEE K, CHUO F, et al. Body mass index as a determinant of systemic exposures to gallotannin metabolites during sixweek consumption of Mango (Mangifera indica L.) modulation of intestinal microbiota in lean and obese individuals [J] . Mol Nutrit Food Res, 2019, 63(2):e1800512.
[16] CHEN K L, MADAK-ERDOGAN Z. Estrogen and microbiota crosstalk: should we pay attention?[J] . Trends Endocrinol Metabol, 2016, 27(11):752-755.
[17] WANG F, YU P, GUI X, et al. Sialoglycoprotein isolated from the eggs of Carassius auratus prevents bone loss: an effect associated with the regulation of gut microbiota in ovariectomized rats[J] . Food Function, 2016, 7(12):4764-4774.
[18] JIN G, ASOU Y, ISHIYAMA K, et al. Proanthocyanidin-rich grape seed extract modulates intestinal microbiota in ovariectomized mice[J] . J Food Sci, 2018, 83(4):1149-1152.
[19] LEE D H, MIN J K, SONG E J, et al. Nutrikinetic study of genistein metabolites in ovariectomized mice[J] . PLoS One, 2017, 161(10):83-93.
[20] DA-HYE L, JUNG K M, SO-HYUN P, et al. Bioavailability of isoflavone metabolites after Korean fermented soybean paste (Doenjang) ingestion in estrogen-deficient rats[J] . J Food Sci, 2018, 83(8):2212-2221.
[21] CAMPOS A C, ROCHA N P, NICOLI J R, et al. Absence of gut microbiota influences lipopolysaccharide-induced behavioral changes in mice[J] . Behav Brain Res, 2016, 312: 186-194.
[22] HOBAN A E, MOLONEY R D, GOLUBEVA A V, et al. Behavioural and neurochemical consequences of chronic gut microbiota depletion during adulthood in the rat[J] . Neuroscience, 2016, 339: 463-477.
[23] ZHANG L, LI F, QIN W J, et al. Changes in intestinal microbiota affect metabolism of ginsenoside Re[J] . Biomed Chromatogr Bmc, 2018, 83: 1444-1453.
[24] ALOLGA R N, FAN Y, CHEN Z, et al. Significant pharmacokinetic differences of berberine are attributable to variations in gut microbiota between Africans and Chinese[J] . Sci Rep, 2016, 6(1):27671-27679.
[25] LIU B, ZHANG Y, RONG W, et al. Western diet feeding influences gut microbiota profiles in apoE knockout mice[J] . Lipids Health Dis, 2018, 17(1):159-167.
[26] WAN J Y, WANG C Z, ZHANG Q H, et al. Significant difference in active metabolite levels of ginseng in humans consuming Asian or Western diet: the link of enteric microbiota[J] . Biomed Chromatogr, 2017, 31(4):3851-3872.
[27] O′TOOLE P W, JEFFERY I B. Gut microbiota and aging[J] . Science, 2015, 350(6265):1214-1215.
[28] LINDAY L, DOBKIN J F, WANG T C, et al. Digoxin inactivation by the gut flora in infancy and childhood[J] . Pediatrics, 1987,79(4):544-548.
[29] YIN J J, ZHOU B J. Research progress of pharmacokinetics of traditional Chinese medicine compound prescription[J] . J China Pharm(中国药房), 2012, 23(47):4503-4505.
[30] YU J, GUO J, TAO W, et al. Gancao-Gansui combination impacts gut microbiota diversity and related metabolic functions[J] . J Ethnopharm, 2017, 214: 71-82.
[31] SHAN J J, ZOU J S, XIE T, et al. Effects of Gancao on pharmacokinetic profiles of platycodin D and deapio-platycodin D in Jiegeng[J] . J Ethnopharm, 2015, 170: 50-56.
[32] LE B Q, WARD T, SIDIROPOULOS D, et al. Fecal microbiota transplantation reverses antibiotic and chemotherapy-induced gut dysbiosis in mice[J] . Sci Rep, 2018, 8(1):6219-6230.
[33] KIM I S, YOO D H, JUNG L H, et al. Reduced metabolic activity of gut microbiota by antibiotics can potentiate the antithrombotic effect of aspirin[J] . Bioche Pharm, 2016, 122: 72-79.
[34] YOO H H, KIM I S, YOO D H, et al. Effects of orally administered antibiotics on the bioavailability of amlodipine: gut microbiota-mediated drug interaction[J] . J Hypert, 2016, 34(1):156-162.
[35] XU R, PENG Y, WANG M, et al. Effects of broad-spectrum antibiotics on the metabolism and pharmacokinetics of ginsenoside Rb1: a study on rats? gut microflora influenced by lincomycin[J] . J Ethnopharm, 2014, 158: 338-344.
[36] GOLDIN B R, GORBACH S L. Clinical indications for probiotics: an overview[J] . Clin Infect Dis Off Pub Infect Dis Soc Aam, 2008, 46(2):96-100.
[37] BRON P A, MICHIEL K, ROBERT-JAN B, et al. Can probiotics modulate human disease by impacting intestinal barrier function?[J] . Br J Nut, 2017, 117(1):1-15.
[38] WASILEWSKI A, ZIELIN′SKA M, STORR M, et al. Beneficial effects of probiotics, prebiotics, synbiotics, and psychobiotics in inflammatory bowel disease[J] . Inflam Bowel Dis, 2015, 21(7):1674-1682.
[39] LEE S H, AN J H, LEE H J, et al. Evaluation of pharmacokinetic differences of acetaminophen in pseudo germ-free rats[J] . Biopharm Drug Dis, 2012, 33(6):292-303.
[40] STOJANEVIC′ M, BOJIC′ G, SALAMI H A, et al. The influence of intestinal tract and probiotics on the fate of orally administered drugs[J] . Curr Issu Mol Bio, 2014, 16(2):55-68.
[41] KIM J K, CHOI M S, JEONG J J, et al. Effect of probiotics on pharmacokinetics of orally administered acetaminophen in mice[J] . Drug Metab Dispos, 2018, 46(2):122-130.
[42] ZHANG Q, ZHANG S, MENG X X, et al. Effects of intestinal flora imbalance on pharmacokinetic parameters of baicalin and baicalein in rats[J] . Chin Tradit Herb Drugs(中草药),2017, 48(18):3783-3788.

基金

国家自然科学基金项目资助(81773862,81573584)
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