PD parameters adjusted for free drug concentration after 5 days of daily administration of study drugsa

Drug and treatment regimenNo. of patientsCmax (μg/ml)AUC0-12 (μg·h/ml)AUC0-24 (μg·h/ml)MIC (μg/ml)Cmax/MIC (IQRb)AUC0-12 /MIC (IQR)AUC0-24 /MIC (IQR)% Dosing interval above MICc (IQR)
Linezolid (600 mg twice daily)913.4 (8.1-17.2)80.3 (34.8-136.1)160.7 (134.4-225.8)1.0 (0.5-1.0)16.2 (14.3-23.0)121.6 (79.8-141.6)243.2 (159.7-283.2)100.0 (100-100)
Linezolid (600 mg once daily)1010.3 (8.2-14.7)60.1 (32.8-82.3)66.8 (33.0-99.2)0.5 (0.5-1.0)20.0 (10.2-21.9)107.8 (63.4-126.3)116.2 (71.0-138.4)62.8 (54.6-77.0)
  • a Cmax and AUC data represent median (range) values for unbound (free) drug in plasma. Linezolid was assumed to be 31% protein bound. Median (range) values for Cmax/MIC, AUC0-12/MIC, AUC0-24/MIC, and percent dosing interval above MIC were calculated using the measured linezolid MIC for a pretreatment sputum M. tuberculosis isolate from each patient. Data for AUC0-24 and AUC0-24/MIC represent simulated median (range) values to reflect the impact of a second daily dose of linezolid.

  • b IQR, interquartile range.

  • c Determined by linear extrapolation of AUC data to intersection with MIC. Data for twice-daily treatment group represent a 12-h interval; data for once-daily treatment group represent a 24-h interval.