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Antimicrob Agents Chemother. 2013 Oct;57(10):5138-40. doi: 10.1128/AAC.00918-13. Epub 2013 Jul 15.

Pharmacokinetic and in vivo efficacy studies of the mycobactin biosynthesis inhibitor salicyl-AMS in mice.

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1
Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Abstract

Mycobactin biosynthesis in Mycobacterium tuberculosis facilitates iron acquisition, which is required for growth and virulence. The mycobactin biosynthesis inhibitor salicyl-AMS [5'-O-(N-salicylsulfamoyl)adenosine] inhibits M. tuberculosis growth in vitro under iron-limited conditions. Here, we conducted a single-dose pharmacokinetic study and a monotherapy study of salicyl-AMS with mice. Intraperitoneal injection yielded much better pharmacokinetic parameter values than oral administration did. Monotherapy of salicyl-AMS at 5.6 or 16.7 mg/kg significantly inhibited M. tuberculosis growth in the mouse lung, providing the first in vivo proof of concept for this novel antibacterial strategy.

PMID:
23856770
PMCID:
PMC3811451
DOI:
10.1128/AAC.00918-13
[Indexed for MEDLINE]
Free PMC Article
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