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

Abstract

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.

Herb-drug Pharmacokinetic Interaction between Carica Papaya Extract and Amiodarone in Rats

“…Even so, it should be taken in account that results from animal experiments cannot be directly extrapolated to humans; however, bearing in mind the studies of Meng et al (55) and Shayeganpour et al (36), the rat appears to be an appropriate model for man in this case. Indeed, the mean peak plasma concentrations of amiodarone achieved in our work (Cmax 1.38 μg/mL and 0.95 μg/mL) are within the established drug therapeutic range (0.5-2 µg/mL) (36,37) and such concentrations were only slightly higher than the levels found in other studies performed in Wistar rats with same dosage (50 mg/kg) of amiodarone (Cmax 0.78 μg/mL and 0.84 μg/mL) (56).…”

Drug–gut microbiota interactions: implications for neuropharmacology

“…The pharmacokinetics of an oral hypoglycaemic agent, gliclazide (administered as a single dose at 20 mg·kg −1 ), was significantly altered in diabetic rats pretreated with a cocktail of three probiotics ( Lactobacillus acidophilus , Lactobacillus rhamnosus and Bifidobacterium lactis ) for 3 days (Al‐Salami et al ., ). Similarly, probiotic treatment significantly altered the absorption of the anti‐arrhythmic agent amiodarone (Matuskova et al ., ). In this study, the probiotic E. coli strain Nissile (EcN) 1917 was administered to rats for 7 days, prior to a single p.o.…”

How Probiotics Affect the Microbiota

“…The E. coli strain Nissle 1917 increased amiodarone bioavailability in rats, while probiotic strains of L. casei slowed, although non-significantly, amiodarone absorption (Matuskova et al, 2014(Matuskova et al, , 2017. Kim et al showed that oral administration of L. reuteri K8 to mice reduced the area under the curve of acetaminophen compared with that of control mice (Kim et al, 2018).…”