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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...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2019
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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. |
format | Online Article Text |
id | pubmed-6945238 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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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