Administration of a probiotic can change drug pharmacokinetics: effect of E. coli Nissle 1917 on amidarone absorption in rats

PLoS One. 2014 Feb 5;9(2):e87150. doi: 10.1371/journal.pone.0087150. eCollection 2014.


The growing interest in the composition and effects of microbiota raised the question how drug pharmacokinetics could be influenced by concomitant application of probiotics. The aim of this study was to find whether probiotic E. coli strain Nissle 1917 (EcN) influences the pharmacokinetics of concomitantly taken antiarrhythmic drug amiodarone (AMI). Live bacterial suspension of probiotic EcN (or non-probiotic E. coli strain ATCC 25922) was applied orally to male Wistar rats for seven days, while a control group of rats was treated with a saline solution. On the eighth day, the amiodarone hydrochloride was administered as one single oral dose (50 mg/kg) to all rats (N = 60). After 0, 1, 2, 3, 4, 5.5, 7, 9, 14, 22, and 30 hours, blood samples were taken from the rat abdominal aorta. The plasma level of AMI and its metabolite N-desethylamiodarone (DEA) was determined using the HPLC with UV detection. Administration of EcN led to a 43% increase of AMI AUC0-30 in comparison with control samples. However, this effect was not observed if EcN was replaced by a reference non-probiotic E. coli strain. Thus, EcN administration was most probably responsible for better drug absorption from the gastrointestinal tract. Plasma levels of DEA were also increased in plasma samples from animals treated with EcN. This change was again not found in the experiment with the reference non-probiotic strain. Higher DEA levels in samples from EcN-treated rats may be explained either by better absorption of AMI and/or by an increased activity of CYP2C forms, known to participate in metabolism of this drug, after EcN administration. In this paper, it is documented that concomitantly taken probiotic EcN may modulate pharmacokinetics of a drug; in this case, it led to an increased bioavailability of AMI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amiodarone / pharmacokinetics*
  • Amiodarone / pharmacology
  • Animals
  • Anti-Arrhythmia Agents / pharmacokinetics*
  • Anti-Arrhythmia Agents / pharmacology
  • Cytochrome P-450 Enzyme System / metabolism
  • Escherichia coli*
  • Gastrointestinal Tract / metabolism*
  • Gastrointestinal Tract / microbiology*
  • Male
  • Probiotics / pharmacology*
  • Rats
  • Rats, Wistar


  • Anti-Arrhythmia Agents
  • cytochrome P-450 CYP2C subfamily
  • Cytochrome P-450 Enzyme System
  • Amiodarone

Grant support

The authors gratefully acknowledge financial support from Czech Science Foundation (P303/12/0535, P303/12/G163, P304/11/1252), IGA Ministry of Health of the Czech Republic (NT 13482-4/2012) as well as of the students' project IGA UPOL LF_2013_007 is gratefully acknowledged. Infrastructural part of this work (at the Institute of Molecular and Translational Medicine) was supported from the Operational Programme Research and Development for Innovations (CZ.1.05/2.1.00/01.0030). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.