Effectiveness of nitroimidazooxazines indicated that although PA 824 was not the most active compound against in vitro grown Mtb from your first line under investigation, in vivo studies showed that it is the most active compound in infected rats. The suitability of PA 824 in changing standard anti tubercular drugs in the initial or continuation pan Chk inhibitor phases of TB chemotherapy is examined in many studies in mice where standard treatment includes an initial 2 months of RIF/pyrazinamide / INH accompanied by a continuation phase with RIF/INH. It’s been established that PA 824 isn’t additive or synergistic to INH in the first intense 2 month treatment period, although, as expected, its mixture with INH did prevent the emergence of INH resistance. Followup studies to investigate the power of PA 824 in replacing drugs in standard drug combination regimens, proved that PA 824 can replace, and was notably greater than, extension phases of therapy as well as INH in the intensive. But, it was found that it could not replace PZA in the two month Meristem intensive phase and that RIF was important in most drug combos with PA 824 in the intensive in addition to continuation phases of therapy. There clearly was no statistically significant difference, but, in the percentage of rats relapsing after six months of treatment in drug mixtures containing PA 824 preventing any results to be manufactured as to the energy of PA 824 in reducing standard therapy, even though, as recognized in this study, the difference between murine and human TB makes direct extrapolation of results from mouse studies to human treatment difficult. More extensive studies showed that PA 824, in combination with PZA, Fostamatinib R788 confirmed synergistic bactericidal action in the murine model of TB with similar potency to the common anti TB regimen of PZA, RIF and INH. Moreover, this study demonstrated that substitution of INH in standard programs with 100 mg/kg of PA 824 led to apparent sanitation of organs after only 2 months of treatment and with no evidence of relapse seen 4 months after cessation of treatment. Nuermberger et al. also investigated novel drug combinations in the search of therapies that might significantly reduce the period of chemotherapy. They found that PA 824 in conjunction with moxifloxacin and PZA could cure mice quicker than INH, RIF and PZA and that 2 months of PA 824/moxifloxacin/PZA followed by 2 months of PA 824/moxifloxacin led to apparent cure as seen by the absence of relapse 3 months after cessation of treatment. In addition, in an effort to improve the effectiveness of PA 824, solutions to allow pulmonary supply were developed as a way to launch substance at the website of infection. A formulation of 1,2 dipalmitoyl sn glycero and PA 824, M leucine 3 phosphocholine in 70-80 ethanol was spray dried to make porous particles suitable for aerosolization.