Verapamil increases the bactericidal activity of bedaquiline against Mycobacterium tuberculosis in a mouse model

Antimicrob Agents Chemother. 2015 Jan;59(1):673-6. doi: 10.1128/AAC.04019-14. Epub 2014 Oct 20.

Abstract

Bedaquiline is a newly approved drug for the treatment of multidrug-resistant tuberculosis, but there are concerns about its safety in humans. We found that the coadministration of verapamil with subinhibitory doses of bedaquiline gave the same bactericidal effect in mice as did the full human bioequivalent bedaquiline dosing. Adding verapamil to bedaquiline monotherapy also protected against the development of resistant mutants in vivo. The adjunctive use of verapamil may permit use of lower doses of bedaquiline to be used and thereby reduce its dose-related toxicities in tuberculosis patients.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antitubercular Agents / administration & dosage
  • Antitubercular Agents / pharmacology
  • Antitubercular Agents / therapeutic use*
  • Calcium Channel Blockers / administration & dosage
  • Calcium Channel Blockers / pharmacology
  • Calcium Channel Blockers / therapeutic use*
  • Diarylquinolines / administration & dosage
  • Diarylquinolines / pharmacology
  • Diarylquinolines / therapeutic use*
  • Disease Models, Animal
  • Drug Synergism
  • Drug Therapy, Combination
  • Female
  • Lung / microbiology
  • Mice
  • Mice, Inbred BALB C
  • Mycobacterium tuberculosis / drug effects*
  • Tuberculosis, Pulmonary / drug therapy*
  • Tuberculosis, Pulmonary / microbiology
  • Verapamil / administration & dosage
  • Verapamil / pharmacology
  • Verapamil / therapeutic use*

Substances

  • Antitubercular Agents
  • Calcium Channel Blockers
  • Diarylquinolines
  • bedaquiline
  • Verapamil