Effects of a rifampicin pre-treatment on linezolid pharmacokinetics

Fumiyasu Okazaki; Yasuhiro Tsuji; Yoshihiro Seto; Chika Ogami; Yoshihiro Yamamoto; Hideto To

doi:10.1371/journal.pone.0214037

Effects of a rifampicin pre-treatment on linezolid pharmacokinetics

PLoS One. 2019 Sep 13;14(9):e0214037. doi: 10.1371/journal.pone.0214037. eCollection 2019.

Authors

Fumiyasu Okazaki¹, Yasuhiro Tsuji², Yoshihiro Seto¹, Chika Ogami¹, Yoshihiro Yamamoto³, Hideto To¹

Affiliations

¹ Department of Medical Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
² Center for Pharmacist Education, School of Pharmacy, Nihon University, Chiba, Japan.
³ Department of Clinical Infectious Diseases, Graduate School of Medicine and Pharmaceutical Sciences for Research University of Toyama, Toyama, Japan.

Abstract

Linezolid is an oxazolidinone antibiotic that effectively treats methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE). Since rifampicin induces other antibiotic effects, it is combined with linezolid in therapeutic regimes. However, linezolid blood concentrations are reduced by this combination, which increases the risk of the emergence of antibiotic-resistant bacteria. We herein demonstrated that the combination of linezolid with rifampicin inhibited its absorption and promoted its elimination, but not through microsomal enzymes. Our results indicate that the combination of linezolid with rifampicin reduces linezolid blood concentrations via metabolic enzymes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibiotics, Antitubercular / pharmacokinetics
Antibiotics, Antitubercular / pharmacology*
Cytochrome P-450 CYP3A / genetics
Cytochrome P-450 CYP3A / metabolism
Drug Interactions
Humans
Linezolid / pharmacokinetics*
Liver / metabolism
Male
Methicillin-Resistant Staphylococcus aureus / drug effects
Mice
Microbial Sensitivity Tests
Rifampin / pharmacology*
Staphylococcal Infections / drug therapy
Staphylococcal Infections / microbiology

Substances

Antibiotics, Antitubercular
Cytochrome P-450 CYP3A
Linezolid
Rifampin

Grants and funding

This work was supported by Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant number 17K08438. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.