Accumulation of TB-Active compounds in murine organs relevant to infection by mycobacterium tuberculosis

Lloyd Tanner, Richard K. Haynes, Lubbe Wiesner

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)
35 Downloads (Pure)

Abstract

Tuberculosis (TB), the leading cause of death due to an infectious agent, requires prolonged and costly drug treatments. With the rise in incidence of MDR and XDR TB, newer more efficacious treatments which are better able to permeate into the deeper recesses of the human lung where bacteria reside are urgently required. To this end, two new promising drug candidates, the decoquinate derivative RMB041 and the phenoxazine PhX1, were assessed for their abilities to permeate into specific murine organs. In particular, PhX1 permeation into the lungs and heart was notably efficient, as reflected in the high relative AUC values of 9669 ± 120.2 min/nmol/mg and 12450 ± 45.2 min/nmol/mg for lung and heart tissue, respectively. However, neither compound maintained a free concentration in the lung which exceeded the compound’s respective MIC90 values, indicating the importance of correcting for organ specific binding.

Original languageEnglish
Article number724
Number of pages8
JournalFrontiers in Pharmacology
Volume11
DOIs
Publication statusPublished - 19 May 2020

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