Administration of a Probiotic Can Change Drug Pharmacokinetics: Effect of E. coli Nissle 1917 on Amidarone Absorption in Rats

0428339 - MBÚ 2015 RIV US eng J - Článek v odborném periodiku
Matusková, Z. - Anzenbacherová, E. - Večeřa, R. - Tlaskalová-Hogenová, Helena - Kolář, M. - Anzenbacher, P.
Administration of a Probiotic Can Change Drug Pharmacokinetics: Effect of E. coli Nissle 1917 on Amidarone Absorption in Rats.
PLoS ONE. Roč. 9, č. 2 (2014). ISSN 1932-6203. E-ISSN 1932-6203
Grant CEP: GA ČR GAP303/12/0535; GA ČR(CZ) GAP304/11/1252; GA MZd(CZ) NT13483
Institucionální podpora: RVO:61388971
Klíčová slova: STRAIN NISSLE-1917 * GUT MICROBIOTA * AMIODARONE
Kód oboru RIV: EC - Imunologie
Impakt faktor: 3.234, rok: 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 AUC(0-30) 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
Trvalý link: http://hdl.handle.net/11104/0233698