Trial reportAntimicrobial agents and chemotherapy2011
Biomarker-assisted dose selection for safety and efficacy in early development of PNU-100480 for tuberculosis.
Trial report in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
52 citing papers in PubMed, 2 syntheses or guidelines pooled it, 128 citations in OpenAlex.
- Development and application of the direct mycobacterial growth inhibition assay: a systematic review.Frontiers in immunology · 2024Pooled it
- Linezolid pharmacokinetics in MDR-TB: a systematic review, meta-analysis and Monte Carlo simulation.The Journal of antimicrobial chemotherapy · 2018Pooled it
- panTB-HM: a multi-arm clinical trial of a pan-TB regimen targeting both host and microbe.Trials · 2026Trial
- Adjunctive use of celecoxib with anti-tuberculosis drugs: evaluation in a whole-blood bactericidal activity model.Scientific reports · 2018Trial
- Trial
- Population Pharmacokinetics of AZD-5847 in Adults with Pulmonary Tuberculosis.Antimicrobial agents and chemotherapy · 2017Trial
- Coadministration of Allopurinol To Increase Antimycobacterial Efficacy of Pyrazinamide as Evaluated in a Whole-Blood Bactericidal Activity Model.Antimicrobial agents and chemotherapy · 2017Trial
- Mycobactericidal activity of sutezolid (PNU-100480) in sputum (EBA) and blood (WBA) of patients with pulmonary tuberculosis.PloS one · 2014Trial
- Article
- Deciphering linezolid-induced hematologic toxicity: Targeting TOP2A and TOP2B via its primary metabolite PNU142586.Science advances · 2025Article
- Neuromyelitis optica causing vision loss during TB treatment with sutezolid: evidence of aberrant immunity following infection.IJTLD open · 2025Article
- Revolutionizing tuberculosis treatment: Breakthroughs, challenges, and hope on the horizon.Acta pharmaceutica Sinica. B · 2025Review
- Comparative In Vitro Drug Susceptibility Study of Five Oxazolidinones AgainstPathogens (Basel, Switzerland) · 2025Article
- New Oxazolidinones for Tuberculosis: Are Novel Treatments on the Horizon?Pharmaceutics · 2024Review
- Next-Generation Diarylquinolines Improve Sterilizing Activity of Regimens with Pretomanid and the Novel Oxazolidinone TBI-223 in a Mouse Tuberculosis Model.Antimicrobial agents and chemotherapy · 2023Article
- Review
- Single Ascending-Dose Study To Evaluate the Safety, Tolerability, and Pharmacokinetics of Sutezolid in Healthy Adult Subjects.Antimicrobial agents and chemotherapy · 2022Article
- Novel oxazolidinones harbor potentFrontiers in medicine · 2022Article
- The pipeline of new molecules and regimens against drug-resistant tuberculosis.Journal of clinical tuberculosis and other mycobacterial diseases · 2021Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tuberculosis is a serious global health threat for which new treatments are urgently needed. This study examined the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple ascending doses of the oxazolidinone PNU-100480 in healthy volunteers, using biomarkers for safety and efficacy. Subjects were randomly assigned to PNU-100480 or placebo (4:1) at schedules of 100, 300, or 600 mg twice daily or 1,200 mg daily for 14 days or a schedule of 600 mg twice daily for 28 days to which pyrazinamide was added on days 27 and 28. A sixth cohort was given linezolid at 300 mg daily for 4 days. Signs, symptoms, and routine safety tests were monitored. Bactericidal activity against Mycobacterium tuberculosis was measured in ex vivo whole-blood culture. Plasma drug and metabolite concentrations were compared to the levels required for inhibition of M. tuberculosis growth and 50% inhibition of mitochondrial protein synthesis. All doses were safe and well tolerated. There were no hematologic or other safety signals during 28 days of dosing at 600 mg twice daily. Plasma concentrations of PNU-100480 and metabolites at this dose remained below those required for 50% inhibition of mitochondrial protein synthesis. Cumulative whole-blood bactericidal activity of PNU-100480 at this dose (-0.316 ± 0.04 log) was superior to the activities of all other doses tested (P < 0.001) and was significantly augmented by pyrazinamide (-0.420 ± 0.06 log) (P = 0.002). In conclusion, PNU-100480 was safe and well tolerated at all tested doses. Further studies in patients with tuberculosis are warranted. Biomarkers can accelerate early development of new tuberculosis treatments.
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