TABLE 2

Lesion PK/PD parameters in rabbits receiving the human-equivalent dose of MXF, LVX, or GTXa

DrugMacIC90
(mg/liter)
MacMBC90
(mg/liter)
WCC
(mg/liter)
CasMBC90
(mg/liter)
Simulated
AUCcellular[0–24]
mean (95% CI)
(mg*h/liter)
Simulated
AUCcaseum[0–24]
mean (95% CI)
(mg*h/liter)
h 2, h 6,
h 12
caseum/cell
ratiob
MXF21643.2609 (584–635)276 (251–301)0.36, 0.79, 0.62
GTX1.516182.2192 (166–218)103 (83–123)0.93, 0.98, 0.51
LVX432184.0325 (259–392)238 (181–295)0.76, 1.16, 1.02
  • a MacIC90 and MacMBC90, MIC90 and MBC90, respectively, against intracellular M. tuberculosis in murine bone marrow-derived macrophages (this work); WCC, Wayne cidal concentration (the concentration which kills 90% of viable bacilli under hypoxia-induced nonreplicating conditions) (from reference 47); casMBC90, MIC90 (1-log kill) against ex vivo M. tuberculosis from cavity caseum; AUCcellular[0–24], area under the concentration-time curve from 0 to 24 h in cellular granulomas at the human-equivalent dose as determined from the computational model; AUCcaseum[0–24], area under the concentration-time curve in caseum; CI, confidence interval.

  • b Data were determined by laser capture microdissection and HPLC coupled to tandem mass spectrometry (55, 67).