Table 1.

Final parameter estimates of the Multistate Tuberculosis Pharmacometric (MTP) model for rifampicin in an acute tuberculosis mouse model

Parameter	Description	Typical Value	RSE (%)
F0 (lungs−1)	Initial number of bacteria in a fast-multiplying bacterial state in treated mice	331000	54.1
F†0 (lungs−1)	Initial number of bacteria in a fast-multiplying bacterial state in untreated mice	8340	8.7
kG (h−1)	Growth rate of the fast-multiplying bacteria	0.0333	4.4
${\text{k}}_{{\text{FS}}_{\text{lin}}}$ (h−2)	Time-dependent transfer rate from fast- to slow-multiplying bacterial states	2.96·10−5	29.8
kSF (h−1)	First-order transfer rate from slow- to fast-multiplying bacterial states	6.04·10−4 FIX*
kFN (h−1)	First-order transfer rate from fast- to non-multiplying bacterial states	3.74·10−8 FIX*
kSN (h−1)	First-order transfer rate from slow- to non-multiplying bacterial states	7.75·10−3 FIX*
kNS (h−1)	First-order transfer rate from non- to slow-multiplying bacterial states	5.12·10−5 FIX*
${\text{FG}}_{{\text{I}}_{\text{MAX}}}$	Maximum achievable fractional rifampicin-induced inhibition of fast-multiplying bacterial growth rate	0.716	16.2
${\text{FG}}_{{\text{IC}}_{50}}$(µg·mL−1)	Rifampicin concentration at 50% of ${\text{FG}}_{{\text{I}}_{\text{MAX}}}$	0.0397	50.2
γ	Sigmoidicity parameter	2.19	7.2
${\text{FD}}_{{\text{E}}_{\text{MAX}}}$ (h−1)	Maximum achievable fractional rifampicin-induced stimulation of fast-multiplying bacterial death rate	352	12.8
${\text{FD}}_{{\text{EC}}_{50}}$ (µg·mL−1)	Rifampicin concentration at 50% of ${\text{FD}}_{{\text{E}}_{\text{MAX}}}$	212	30.4
${\text{SD}}_{\text{k}}$ (mL·h−1·μg−1)	Second-order slow-multiplying bacterial death rate	4.91·10−3	12.9
Error	Additive residual error variability (variance) on log scale	0.217	12.0

FIX^*: Fixed to estimates from application of the MTP model in vitro [6]

F fast-multiplying bacteria; S slow-multiplying bacteria; N non-multiplying bacteria; RSE relative standard error reported on the approximate standard deviation scale