High rifampicin peak plasma concentrations accelerate the slow phase of bacterial decline in tuberculosis patients: Evidence for heteroresistance
Fig 6
Estimated TSCC based on the statistical analysis, and comparison to measured TSCCs in a multi arm multi stage (MAMS) clinical trial (NCT01785186, [30]).
Here, the green curves show estimates based on biphasic curves (i.e taking the slowdown in decline into account), while red shows estimation based on monophasic curves (i.e. neglecting the possibility of a slowdown in decline). Blue always corresponds to data from the MAMS clinical trial. Fig 5A and 5C show the dependence of the predicted TSCC on the pharmacokinetic parameters (Cmax and AUC respectively), as well as the measured pharmacokinetic ranges for the HR35ZE treatment arm of the MAMS clinical trial used for comparison (blue boxes). Here, the area around the estimates signify the 95% confidence interval around our estimates. The estimates are only shown within the parameter ranges of the EBA clinical trial. Fig 5B and 5D show the cumulative probability (Y-axis) of TSCC (X-axis) based on the estimates within the PK ranges of the MAMS trial as well as the data from the MAMS trial itself.