linezolid and Tuberculosis--Pulmonary

Nineteen adults with pulmonary tuberculosis received linezolid (600 mg) once or twice daily in an early bactericidal activity trial. A one-compartment population model produced median values for the absorption rate constant, volume of distribution, and elimination rate constant of 1.5 h(-1), 29.6 liters, and 0.25 h(-1) (once daily) and 2.7 h(-1), 32.1 liters, and 0.15 h(-1) (twice daily). Linezolid administered twice daily produced higher values for free drug area under the concentration-time curve (AUC)/MIC and time above MIC. Both regimens achieved free AUC/MIC ratios > 100. Median times above the MIC for free drug were 100% (twice daily) and 63% (once daily).

Topics: Acetamides; Adolescent; Adult; Anti-Bacterial Agents; Drug Administration Schedule; Female; Humans; Linezolid; Male; Middle Aged; Oxazolidinones; Tuberculosis, Pulmonary; Young Adult

Murine models of Mycobacterium tuberculosis infection are essential tools in drug discovery. Here we describe a fast standardized 9-day acute assay intended to measure the efficacy of drugs against M. tuberculosis growing in the lungs of immunocompetent mice. This assay is highly reproducible, allows good throughput, and was validated for drug lead optimization using isoniazid, rifampin, ethambutol, pyrazinamide, linezolid, and moxifloxacin.

Topics: Acetamides; Animals; Antitubercular Agents; Aza Compounds; Disease Models, Animal; Drug Discovery; Ethambutol; Fluoroquinolones; Immunocompetence; Inhalation Exposure; Isoniazid; Linezolid; Mice; Mice, Inbred C57BL; Moxifloxacin; Oxazolidinones; Pyrazinamide; Quinolines; Reproducibility of Results; Rifampin; Tuberculosis, Pulmonary