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Effect of Lactobacillus casei on the Pharmacokinetics of Amiodarone in Male Wistar Rats

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Abstract

Background and Objectives

The probiotic bacterium Escherichia coli strain Nissle 1917 has previously been shown to alter the pharmacokinetics of amiodarone. The aim of this study was to determine whether the probiotic bacterium Lactobacillus casei produces similar alterations in amiodarone disposition.

Methods

A suspension of live probiotic bacteria L. casei strain DN-114 001 (1.5 × 109 CFU/dose; probiotic pre-treated group) or a saline solution (control group) was administered directly into the stomach of male Wistar rats (N = 30 in each group) by oral gavage daily for 7 consecutive days. On the eighth day, all rats (N = 60) were given a single oral dose of an amiodarone hydrochloride suspension (model drug; 50 mg/kg). The concentrations of amiodarone and of its main metabolite N-desethylamiodarone were determined in rat plasma by high-performance liquid chromatography.

Results

Comparison of the pharmacokinetics of amiodarone in the control group and probiotic pre-treated group revealed that the peak plasma concentration of amiodarone was delayed by >2 h in the probiotic pre-treated group. The plasma level of N-desethylamiodarone was unchanged in the probiotic pre-medicated group and its pharmacokinetic parameters were not altered.

Conclusions

The slower absorption of amiodarone in the probiotic pre-treated rats compared to the control ones and the unchanged pharmacokinetics of its main metabolite suggest that the probiotic strain of L. casei DN-114 001 has probably no clinical consequences as the difference was not statistically significant.

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Acknowledgments

Financial support from the Grant Agency of the Czech Republic P303/12/0535 to Pavel Anzenbacher, Eva Anzenbacherova, Zuzana Matuskova, and Helena Tlaskalova-Hogenova, as well as from the infrastructural projects NPU I (LO1304) and POSTUP II (CZ.1.07/2.3.00/30.0041) of the faculty, which enabled us to conduct the study described here, is gratefully acknowledged.

Compliance with Ethical Standards

All procedures performed in studies involving animals are in accordance with the ethical standards of the Czech Republic Act No. 359/2012 Coll. on the protection of animals and were approved by the Ethics Committee, Ministry of Education, Czech Republic.

Conflict of interest

All authors participating in this paper declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hnevotinska 3, 775 15, Olomouc, Czech Republic

    Zuzana Matuskova, Pavel Anzenbacher, Rostislav Vecera, Michal Siller & Jan Strojil

  2. Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hnevotinska 5, 779 00, Olomouc, Czech Republic

    Zuzana Matuskova, Pavel Anzenbacher & Michal Siller

  3. Institute of Microbiology, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20, Prague, Czech Republic

    Helena Tlaskalova-Hogenova

  4. Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hnevotinska 3, 775 15, Olomouc, Czech Republic

    Eva Anzenbacherova

Authors
  1. Zuzana Matuskova
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  2. Pavel Anzenbacher
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  3. Rostislav Vecera
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  4. Michal Siller
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  5. Helena Tlaskalova-Hogenova
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  6. Jan Strojil
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  7. Eva Anzenbacherova
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Correspondence to Eva Anzenbacherova.

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Matuskova, Z., Anzenbacher, P., Vecera, R. et al. Effect of Lactobacillus casei on the Pharmacokinetics of Amiodarone in Male Wistar Rats. Eur J Drug Metab Pharmacokinet 42, 29–36 (2017). https://doi.org/10.1007/s13318-015-0315-0

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  • DOI: https://doi.org/10.1007/s13318-015-0315-0

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