text: Pharmacokinetic-pharmacodynamic analysis.
  The mean (90% CI) slope estimate from the linezolid concentration-R-R interval analysis was -0.0017 (-0.0022 to -0.0011) ms/ng/ml. This translates to mean (90% CI) predicted decreases in heart rate of approximately 1.5 (1.0 to 2.0) and 3.0 (2.1 to 4.1) beats/min at the mean Cmax following the administration of 600- and 1,200-mg linezolid doses, respectively.
  The study-specific mean correction factor estimated from baseline data was 0.278, which is slightly less than Fridericia's correction (0.333). Evaluation of the various correction factors showed that QTcF most appropriately resolves the relationship between the QT interval and the heart rate in the baseline data from the present study. This is evident upon inspection of Fig. 4, since the slope between the QTcF interval and the R-R interval is closest to zero when this correction is applied.
  Fig. 4.
  Evaluation of various heart rate correction factors for the QT interval versus the R-R interval. The predicted line in each figure represents the fit from a linear mixed-effect model with R-R interval as a fixed effect and subject-specific random effects for intercept and slope.
  The results from the concentration-QTcF analysis are graphically depicted in Fig. 5. The mean (90% CI) slope estimate from the linezolid concentration-QTcF analysis was -0.0145 (-0.0768 to 0.0477) ms/mug/ml. At the geometric mean Cmax following the infusion of linezolid at 600 mg (14.9 mug/ml) and 1,200 mg (30.5 mug/ml), the mean (90% CI) predicted placebo-adjusted changes from the baseline QTcF were -0.217 (-1.14 to 0.710) and -0.444 (-2.34 to 1.45) ms, respectively, thus confirming a lack of a relationship between linezolid concentrations and QTc interval.
  Fig. 5.
  QTcF interval versus plasma linezolid concentrations.
  
entities.text: ['heart']
entities.type: Organ
entities.entity_id: PMC-3165302-sec-13_T1
entities.text: ['heart']
entities.type: Organ
entities.entity_id: PMC-3165302-sec-13_T2
entities.text: ['heart']
entities.type: Organ
entities.entity_id: PMC-3165302-sec-13_T3
entities.text: ['plasma']
entities.type: Organism_substance
entities.entity_id: PMC-3165302-sec-13_T4