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Issue 22, 2018, Issue in Progress
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Bedaquiline has potential for targeting tuberculosis reservoirs in the central nervous system

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Abstract

Bedaquiline (BDQ) is the first-in-class United States Food and Drug Administration (US FDA) approved anti-tuberculosis (anti-TB) drug, which is a novel diarylquinoline antibiotic that has recently been utilized as an effective adjunct to existing therapies for multidrug-resistant tuberculosis (MDR-TB). BDQ is especially promising due to its novel mechanism of action, activity against drug-sensitive and drug-resistant tuberculosis (TB) in addition to having the potential to shorten treatment duration. Drug delivery to the central nervous system (CNS) is a major concern in TB chemotherapy, especially with the increasing cases of CNS-TB. In this study, we investigated the CNS penetration of BDQ in healthy rodent brain. Male Sprague-Dawley rats (n = 27; 100 ± 20 g) received a single 25 mg kg−1 b.w dose of BDQ via intraperitoneal (i.p.) administration, over a 24 h period. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine whole tissue drug concentrations and matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) was utilized to evaluate drug distribution in the brain. BDQ reached peak concentrations (Cmax) of 134.97 ng mL−1 in the brain at a Tmax of 4 h, which is within the range required for therapeutic efficacy. BDQ was widely distributed in the brain, with a particularly high intensity in the corpus callosum and associated subcortical white matter including the striatal, globus pallidus, corticofugal pathways, ventricular system, basal forebrain region and hippocampal regions. Using MALDI MSI, this study demonstrates that due to BDQ's distribution in the brain, it has the potential to target TB reservoirs within this organ.

Graphical abstract: Bedaquiline has potential for targeting tuberculosis reservoirs in the central nervous system

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Supplementary files

Article information


Submitted
31 Jan 2018
Accepted
05 Mar 2018
First published
28 Mar 2018

This article is Open Access

RSC Adv., 2018,8, 11902-11907
Article type
Paper

Bedaquiline has potential for targeting tuberculosis reservoirs in the central nervous system

A. Pamreddy, S. Baijnath, T. Naicker, S. Ntshangase, S. Mdanda, H. Lubanyana, H. G. Kruger and T. Govender, RSC Adv., 2018, 8, 11902
DOI: 10.1039/C8RA00984H

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    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
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    [Original citation] - Published by The Royal Society of Chemistry.

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