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Over three million people die from tuberculosis (TB) every year, and drug resistance is an increasing problem. This paper reports the development of a promising new anti-TB agent, R207910, a diarylquinoline. It acts as an inhibitor of mycobacterial ATP synthase, a different mechanism of action from any other anti-TB drug. This minimises the potential for cross-resistance and suggests that R207910 may prove effective in the treatment of MDR-TB, as demonstrated by the authors in vitro. It is specific in activity to mycobacteria, including the opportunistic species MAC and M kansasii, with in vivo bactericidal activity against M tuberculosis in a murine model.
Animal and human pharmacokinetic and pharmacodynamic studies show that R207910 has a long plasma half life, good tissue penetration, and potential for a dose regimen of less than five doses per week, making it ideal for DOT. Human studies have so far shown good tolerability to a treatment dose with no major adverse events.
The authors have shown that R207910 is an effective antimycobacterial agent with pharmacokinetic properties favouring good treatment adherence. It remains to be seen if these results are confirmed in clinical trials.
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