Table 1.

Parameter estimates of the final multistate tuberculosis pharmacometric model applied to cfu data from rifampicin log- and stationary-phase M. tuberculosis H37Rv cultures

Parameter	Estimate	RSE (%)
$k_{\mathrm{FN}}$a (days−1)	0.897 × 10−6	1.2
$k_{\mathrm{SN}}$a (days−1)	0.186	4.3
$k_{\mathrm{SF}}$a (days−1)	0.0145	4.9
$k_{\mathrm{NS}}$a (days−1)	0.123 × 10−2	2.7
$k_{{\mathrm{FS}}_{\mathrm{Lin}}}$a,b (days−2)	0.166 × 10−2	1.6
$S_0$a (mL−1)	9770	2.4
$k_{\mathrm{G}}$a,c (days−1)	0.206	1
$k_{{\mathrm{G}}_{\mathrm{Log}}}$a (days−1)	0.102	12.5
$F_0$a (mL−1)	4.1	2.9
$F_{0_{\mathrm{Log}}}$a (mL−1)	674 × 103	39.2
$B_{\max }$a (mL−1)	242 × 106	4.5
$B_{{\max }_{\mathrm{Stationary}}}$a (mL−1)	1410 × 106	0.8
$F{G}_{\mathrm{k}}$ (L·mg−1)	0.017	11.1
$F{D}_{{\mathrm{E}}_{\max }}$ (days−1)	2.15	4.5
$F{D}_{\mathrm{E}{\mathrm{C}}_{50}}$ (mg·L−1)	0.52	9.8
$S{D}_{{\mathrm{E}}_{\max }}$ (days−1)	1.56	4.7
$S{D}_{\mathrm{E}{\mathrm{C}}_{50}}$ (mg·L−1)	13.4	10.4
$N{D}_{\mathrm{k}}$ (L·mg−1·days−1)	0.24	12.6
ωFa (%)	473.3	5.9
Proportional residual error (%)	63.8	7.8

k_FN, first-order transfer rate between fast- and non-multiplying state; k_SN, first-order transfer rate between slow- and non-multiplying state; k_SF first-order transfer rate between slow- and fast-multiplying state; k_NS, first-order transfer rate between non- and slow-multiplying state, S₀ initial slow-multiplying state bacterial number; k_G, growth rate of the fast multiplying state bacteria; ${{\text{k}}_{\mathrm{G}}}_{\mathrm{Log}},$growth rate of the fast-multiplying state bacteria in experiments with rifampicin log phase cultures; F₀ initial fast-multiplying state bacterial number; ${\text{F}}_{0_{\mathrm{Log}}},$initial fast-multiplying state bacterial number in experiments with rifampicin log phase cultures; B_max, system carrying capacity; ${\text{B}}_{{\max }_{\mathrm{Stationary}}}$, system carrying capacity in experiments with rifampicin stationary phase cultures; FG_k, linear drug-induced inhibition of fast-multiplying state growth; $\text{F}{\text{D}}_{{\mathrm{E}}_{\max }}$, maximum achievable drug-induced fast-multiplying state kill rate; $\text{F}{\text{D}}_{\mathrm{E}{\mathrm{C}}_{50}}$, concentration at 50% of $\text{F}{\text{D}}_{{\mathrm{E}}_{\max }}$; $\text{S}{\text{D}}_{{\mathrm{E}}_{\max }}$, maximum achievable drug-induced slow-multiplying state kill rate; $\text{S}{\text{D}}_{\mathrm{E}{\mathrm{C}}_{50}}$, concentration at 50% of $\text{S}{\text{D}}_{{\mathrm{E}}_{\max }}$; ND_k, non-multiplying state kill rate; ω_F, variability in F₀ expressed as coefficient of variation; RSE, relative standard error reported on the approximate standard deviation scale.

^aFixed during drug evaluation.

^b$k_{FS}=k_{{FS}_{\mathrm{Lin}}}$.

^c$\text{growth}=F\cdot k_G\cdot \text{log(}{B}_{\max }/F+S+N)$.