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Cited by 306

The DOI matches its Crossref record; 20 of the 20 references it cites were found in a registry or an index.

Preclinical Testing of the Nitroimidazopyran PA-824 for Activity against Mycobacterium tuberculosis in a Series of In Vitro and In Vivo Models

Open access
Lenaerts, Anne J., Gruppo, Veronica, Marietta, Karen S., Johnson, Christine M., Driscoll, Diane K., Tompkins, Nicholas M., Rose, Jerry D., Reynolds, Robert C., Orme, Ian M.·2005·Antimicrobial Agents and Chemotherapy
DOI 10.1128/aac.49.6.2294-2301.2005
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Abstract

This study extends earlier reports regarding the in vitro and in vivo efficacies of the nitroimidazopyran PA-824 against Mycobacterium tuberculosis . PA-824 was tested in vitro against a broad panel of multidrug-resistant clinical isolates and was found to be highly active against all isolates (MIC < 1 μg/ml). The activity of PA-824 against M. tuberculosis was also assessed grown under conditions of oxygen depletion. PA-824 showed significant activity at 2, 10, and 50 μg/ml, similar to that of metronidazole, in a dose-dependent manner. In a short-course mouse infection model, the efficacy of PA-824 at 50, 100, and 300 mg/kg of body weight formulated in methylcellulose or cyclodextrin/lecithin after nine oral treatments was compared with those of isoniazid, rifampin, and moxifloxacin. PA-824 at 100 mg/kg in cyclodextrin/lecithin was as active as moxifloxacin at 100 mg/kg and isoniazid at 25 mg/kg and was slightly more active than rifampin at 20 mg/kg. Long-term treatment with PA-824 at 100 mg/kg in cyclodextrin/lecithin reduced the bacterial load below 500 CFU in the lungs and spleen. No significant differences in activity between PA-824 and the other single drug treatments tested (isoniazid at 25 mg/kg, rifampin at 10 mg/kg, gatifloxacin at 100 mg/kg, and moxifloxacin at 100 mg/kg) could be observed. In summary, its good activity in in vivo models, as well as its activity against multidrug-resistant M. tuberculosis and against M. tuberculosis isolates in a potentially latent state, makes PA-824 an attractive drug candidate for the therapy of tuberculosis. These data indicate that there is significant potential for effective oral delivery of PA-824 for the treatment of tuberculosis.

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Metadata

Authors
Lenaerts, A. J., Gruppo, V., Marietta, K. S., Johnson, C. M., Driscoll, D. K., Tompkins, N. M., Rose, J. D., Reynolds, R. C., & Orme, I. M.
Venue
Antimicrobial Agents and Chemotherapy
Publisher
American Society for Microbiology
Published
2005-06
Volume
49
Issue
6
Pages
2294-2301
ISSN
  • 0066-4804 (ISSN-L)
  • 1098-6596
DOI
10.1128/aac.49.6.2294-2301.2005
OpenAlex
W1977671952
Cited by
306
References
20
FWCI
10.20
Type
journal article
Language
en
Open access
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CoChat. (2026). Citation check: Preclinical Testing of the Nitroimidazopyran PA-824 for Activity against Mycobacterium tuberculosis in a Series of In Vitro and In Vivo Models. https://app.cochat.ai/papers/10.1128/aac.49.6.2294-2301.2005
The paper
Lenaerts, A. J., Gruppo, V., Marietta, K. S., Johnson, C. M., Driscoll, D. K., Tompkins, N. M., Rose, J. D., Reynolds, R. C., & Orme, I. M. (2005). Preclinical Testing of the Nitroimidazopyran PA-824 for Activity against Mycobacterium tuberculosis in a Series of In Vitro and In Vivo Models. Antimicrobial Agents and Chemotherapy. https://doi.org/10.1128/aac.49.6.2294-2301.2005

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.