TY - JOUR
T1 - Accumulation of TB-Active compounds in murine organs relevant to infection by mycobacterium tuberculosis
AU - Tanner, Lloyd
AU - Haynes, Richard K.
AU - Wiesner, Lubbe
N1 - Publisher Copyright:
© Copyright © 2020 Tanner, Haynes and Wiesner.
PY - 2020/5/19
Y1 - 2020/5/19
N2 - 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.
AB - 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.
KW - decoquinate
KW - liquid chromatography-tandem mass spectrometry
KW - organ concentrations
KW - phenoxazine
KW - tuberculosis
KW - tuberculosis chemotherapy
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U2 - 10.3389/fphar.2020.00724
DO - 10.3389/fphar.2020.00724
M3 - Article
C2 - 32508649
AN - SCOPUS:85085894822
SN - 1663-9812
VL - 11
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
M1 - 724
ER -