Assessment of carbapenems in a mouse model of Mycobacterium tuberculosis infection.
We present further study of a subset of carbapenems, arising from a previously reported machine learning approach, with regard to their mouse pharmacokinetic profiling and subsequent study in a mouse model of sub-acute Mycobacterium tuberculosis infection. Pharmacokinetic metrics for such small mole...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2021-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0249841 |
| _version_ | 1818825174930161664 |
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| author | Ravindra Jadhav Ricardo Gallardo-Macias Gaurav Kumar Samer S Daher Amit Kaushik Kristina M Bigelow Eric L Nuermberger Gyanu Lamichhane Joel S Freundlich |
| author_facet | Ravindra Jadhav Ricardo Gallardo-Macias Gaurav Kumar Samer S Daher Amit Kaushik Kristina M Bigelow Eric L Nuermberger Gyanu Lamichhane Joel S Freundlich |
| author_sort | Ravindra Jadhav |
| collection | DOAJ |
| description | We present further study of a subset of carbapenems, arising from a previously reported machine learning approach, with regard to their mouse pharmacokinetic profiling and subsequent study in a mouse model of sub-acute Mycobacterium tuberculosis infection. Pharmacokinetic metrics for such small molecules were compared to those for meropenem and biapenem, resulting in the selection of two carbapenems to be assessed for their ability to reduce M. tuberculosis bacterial loads in the lungs of infected mice. The original syntheses of these two carbapenems were optimized to provide multigram quantities of each compound. One of the two experimental carbapenems, JSF-2204, exhibited efficacy equivalent to that of meropenem, while both were inferior to rifampin. The lessons learned in this study point toward the need to further enhance the pharmacokinetic profiles of experimental carbapenems to positively impact in vivo efficacy performance. |
| first_indexed | 2024-12-19T00:07:35Z |
| format | Article |
| id | doaj.art-69535c1c1e5b45e6b864c3a87b820f15 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T00:07:35Z |
| publishDate | 2021-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-69535c1c1e5b45e6b864c3a87b820f152022-12-21T20:46:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-01165e024984110.1371/journal.pone.0249841Assessment of carbapenems in a mouse model of Mycobacterium tuberculosis infection.Ravindra JadhavRicardo Gallardo-MaciasGaurav KumarSamer S DaherAmit KaushikKristina M BigelowEric L NuermbergerGyanu LamichhaneJoel S FreundlichWe present further study of a subset of carbapenems, arising from a previously reported machine learning approach, with regard to their mouse pharmacokinetic profiling and subsequent study in a mouse model of sub-acute Mycobacterium tuberculosis infection. Pharmacokinetic metrics for such small molecules were compared to those for meropenem and biapenem, resulting in the selection of two carbapenems to be assessed for their ability to reduce M. tuberculosis bacterial loads in the lungs of infected mice. The original syntheses of these two carbapenems were optimized to provide multigram quantities of each compound. One of the two experimental carbapenems, JSF-2204, exhibited efficacy equivalent to that of meropenem, while both were inferior to rifampin. The lessons learned in this study point toward the need to further enhance the pharmacokinetic profiles of experimental carbapenems to positively impact in vivo efficacy performance.https://doi.org/10.1371/journal.pone.0249841 |
| spellingShingle | Ravindra Jadhav Ricardo Gallardo-Macias Gaurav Kumar Samer S Daher Amit Kaushik Kristina M Bigelow Eric L Nuermberger Gyanu Lamichhane Joel S Freundlich Assessment of carbapenems in a mouse model of Mycobacterium tuberculosis infection. PLoS ONE |
| title | Assessment of carbapenems in a mouse model of Mycobacterium tuberculosis infection. |
| title_full | Assessment of carbapenems in a mouse model of Mycobacterium tuberculosis infection. |
| title_fullStr | Assessment of carbapenems in a mouse model of Mycobacterium tuberculosis infection. |
| title_full_unstemmed | Assessment of carbapenems in a mouse model of Mycobacterium tuberculosis infection. |
| title_short | Assessment of carbapenems in a mouse model of Mycobacterium tuberculosis infection. |
| title_sort | assessment of carbapenems in a mouse model of mycobacterium tuberculosis infection |
| url | https://doi.org/10.1371/journal.pone.0249841 |
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