Sutezolid (PNU-100480)
Last updated July 2012
ACTIVE TB DISEASE
Sutezolid, or PNU-100480, is a new oxazolidinone—the same class of drugs as linezolid. Sutezolid appears to have more potent antituberculosis activity in vitro, in ex vivo whole blood cultures, and in a murine (mouse) model. A whole-blood study also predicted that sutezolid and two drugs described above—SQ109 and bedaquiline—would be additive, and deserve testing as part of a novel regimen. Pfizer recently completed a phase IIa, open-label, early bactericidal activity and whole-blood activity study. This study of adults with pulmonary DS-TB compared two experimental arms—one with sutezolid twice daily at 600 mg, the other with sutezolid once daily at 1,200 mg—with Rifafour. Results should be available soon.
References:
- Alffenaar JW, van der Laan T, Simons S, et al. Susceptibility of clinical Mycobacterium tuberculosis isolates to a potentially less toxic derivate of linezolid, PNU-100480. Antimicrob Agents Chemother. 2011 Mar;55(3):1287–9. Available from: http://aac.asm.org/content/55/3/1287.full.pdf+html?sid=79a46ebd-2d7b-4075-9633-fc195b37db1b. (Accessed 2012 June 26)
- Wallis RS, Jakubiec W, Kumar V, et al. Biomarker-assisted dose selection for safety and efficacy in early development of PNU-100480 for tuberculosis. Antimicrob Agents Chemother. 2011 Feb;55(2):567–74. Available from: http://aac.asm.org/content/early/2010/11/15/AAC.01179-10.full.pdf. (Accessed 2012 June 26)
- Wallis RS, Jakubiec WM, Kumar V, et al. Pharmacokinetics and whole-blood bactericidal activity against Mycobacterium tuberculosis of single doses of PNU-100480 in healthy volunteers. J Infect. Dis. 2010 Sep 1;202(5):745–51.
- Williams KN, Brickner SJ, Stover CK, et al. Addition of PNU-100480 to first-line drugs shortens the time needed to cure murine tuberculosis. Am J Respir Crit Care Med. 2009 Aug 15;180(4):371–6.
- Williams KN, Stover CK, Zhu T, et al. Promising antituberculosis activity of the oxazolidinone PNU-100480 relative to that of linezolid in a murine model. Antimicrob Agents Chemother. 2009 Apr;53(4):1314–9.
- Wallis RS, Jakubiec W, Mitton-Fry M, et al. Rapid evaluation in whole blood culture of regimens for XDR-TB containing PNU-100480 (sutezolid), TMC207, PA-824, SQ109, and pyrazinamide. PLoS One. 2012;7(1):e30479. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3261206/?tool=pubmed. (Accessed 2012 June 26)
- National Institutes of Health (U.S.). A study of PNU-100480 in newly diagnosed, treatment sensitive patients with pulmonary tuberculosis to assess early bactericidal activity (EBA) and whole blood activity (WBA). Available from: http://www.clinicaltrials.gov/ct2/show/NCT01225640?term=PNU100480&rank=3.