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Impact of the host environment on the antitubercular action of pyrazinamide

Pyrazinamide remains the only drug in the tuberculosis pharmacopeia to drastically shorten first-line therapy from nine to six months. Due to its unparalleled ability to sterilize non-replicating bacilli and reduce relapse rates, PZA is expected to be irreplaceable in future therapies against tuberc...

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Detalles Bibliográficos
Autores principales: Lamont, Elise A., Baughn, Anthony D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945238/
https://www.ncbi.nlm.nih.gov/pubmed/31669220
http://dx.doi.org/10.1016/j.ebiom.2019.10.014
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author Lamont, Elise A.
Baughn, Anthony D.
author_facet Lamont, Elise A.
Baughn, Anthony D.
author_sort Lamont, Elise A.
collection PubMed
description Pyrazinamide remains the only drug in the tuberculosis pharmacopeia to drastically shorten first-line therapy from nine to six months. Due to its unparalleled ability to sterilize non-replicating bacilli and reduce relapse rates, PZA is expected to be irreplaceable in future therapies against tuberculosis. While the molecular target of PZA is unclear, recent pharmacokinetic studies using small animal models and patient samples have highlighted the importance of host metabolism and immune responses in PZA efficacy. Delineating which host factors are important for PZA action will be integral to the design of next-generation therapies to shorten current TB drug regimens as well as to overcome treatment limitations in some patients. In this review, we discuss evidence for influence of the host environment on PZA activity, targets for PZA mechanism of action, recent studies in PZA pharmacokinetics, PZA antagonism and synergy with other first-line anti-TB drugs, and implications for future research.
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spelling pubmed-69452382020-01-09 Impact of the host environment on the antitubercular action of pyrazinamide Lamont, Elise A. Baughn, Anthony D. EBioMedicine Review Pyrazinamide remains the only drug in the tuberculosis pharmacopeia to drastically shorten first-line therapy from nine to six months. Due to its unparalleled ability to sterilize non-replicating bacilli and reduce relapse rates, PZA is expected to be irreplaceable in future therapies against tuberculosis. While the molecular target of PZA is unclear, recent pharmacokinetic studies using small animal models and patient samples have highlighted the importance of host metabolism and immune responses in PZA efficacy. Delineating which host factors are important for PZA action will be integral to the design of next-generation therapies to shorten current TB drug regimens as well as to overcome treatment limitations in some patients. In this review, we discuss evidence for influence of the host environment on PZA activity, targets for PZA mechanism of action, recent studies in PZA pharmacokinetics, PZA antagonism and synergy with other first-line anti-TB drugs, and implications for future research. Elsevier 2019-10-25 /pmc/articles/PMC6945238/ /pubmed/31669220 http://dx.doi.org/10.1016/j.ebiom.2019.10.014 Text en © 2019 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Review
Lamont, Elise A.
Baughn, Anthony D.
Impact of the host environment on the antitubercular action of pyrazinamide
title Impact of the host environment on the antitubercular action of pyrazinamide
title_full Impact of the host environment on the antitubercular action of pyrazinamide
title_fullStr Impact of the host environment on the antitubercular action of pyrazinamide
title_full_unstemmed Impact of the host environment on the antitubercular action of pyrazinamide
title_short Impact of the host environment on the antitubercular action of pyrazinamide
title_sort impact of the host environment on the antitubercular action of pyrazinamide
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945238/
https://www.ncbi.nlm.nih.gov/pubmed/31669220
http://dx.doi.org/10.1016/j.ebiom.2019.10.014
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