Table 1.

Parameter estimates of the final multistate tuberculosis pharmacometric (MTP) model describing in vitro data

Parameter	Description	Estimate [RSE (%)]
		CFU only	CFU + MPN
Natural growth
${k_G}^{a,b}$ (days−1)	Growth rate of the fast multiplying state bacteria	0.206 fix	0.206 fix
${B_{\mathit{max}}}^b$ (mL−1)	System carrying capacity	242 × 106 fix	242 × 106 fix
$B_{max,stationary}$ (mL−1)	System carrying capacity for stationary data	388 × 106 (34)	46 × 106 fix
${{k_{\mathit{FS}}}_{\mathit{Lin}}}^{b,c}$(days−2)	Second-order time dependent transfer rate between fast- and slow-multiplying state	0.166 × 10–2 fix	0.166 × 10–2 fix
${k_{\mathit{FN}}}^b$ (days−1)	First-order transfer rate between fast- and non-multiplying state	0.897 × 10–6 fix	0.897 × 10–6 fix
${k_{\mathit{SN}}}^b$ (days−1)	First-order transfer rate between slow- and non-multiplying state	0.186 fix	0.186 fix
${k_{\mathit{SF}}}^b$ (days−1)	First-order transfer rate between slow- and fast-multiplying state	0.0145 fix	0.0145 fix
${k_{\mathit{NS}}}^b$ (days−1)	First-order transfer rate between non- and slow-multiplying state	0.123 × 10–2 fix	0.123 × 10–2 fix
${F_0}^b$ (mL−1)	Initial fast-multiplying state bacterial number	4.11 fix	4.11 fix
${S_0}^b$ (mL−1)	Initial slow-multiplying state bacterial number	9770 fix	9770 fix
ε (%)	Proportional residual error	41.8 (4.2)	–
Exposure–response relationships
${{\mathit{FG}}_k}^b$ (L·mg−1)	Linear drug induced inhibition of fast-multiplying state growth	0.017 fix	0.017 fix
${{\mathit{FD}}_{E_{\mathit{max}}}}^b$ (days−1)	Maximum achievable drug-induced fast-multiplying state kill rate	2.15 fix	2.15 fix
${{\mathit{FD}}_{{\mathit{EC}}_{50}}}^b$ (mg·L−1)	Concentration at 50% of ${\mathit{FD}}_{E_{\mathit{max}}}$	0.52 fix	0.52 fix
${\mathit{SD}}_{E_{\mathit{max}}}$ (days−1)	Maximum achievable drug-induced slow-multiplying state kill rate	1.56 fix	2.11 (6)
${{\mathit{SD}}_{{\mathit{EC}}_{50}}}^b$ (mg·L−1)	Concentration at 50% of ${\mathit{SD}}_{E_{\mathit{max}}}$	13.4 fix	13.4 fix
${{\mathit{ND}}_k}^b$ (L·mg−1·days−1)	Linear drug induced kill of non-multiplying state	0.24 fix	–
${\mathit{ND}}_{E_{\mathit{max}}}$ (days−1)	Maximum achievable drug-induced non-multiplying state kill rate	–	2.58 (16.4)
${\mathit{ND}}_{{\mathit{EC}}_{50}}$ (mg·L−1)	Concentration at 50% of ${\mathit{ND}}_{E_{\mathit{max}}}$	–	39.42 (34.5)
ε (%)	Proportional residual error	274 (8.3)	79.3 (22.8)

Parameter values are presented as applied to colony forming unit (CFU) only and to CFU plus most probable number (MPN)

dataRSE = relative standard error reported on the approximate standard deviation scale

^a$growth=F·k_G·log\left(\frac{B_{\mathit{max}}}{F+S+N}\right)$

^bfixed to previously published value [14]

^c$k_{\mathit{FS}}={k_{\mathit{FS}}}_{\mathit{Lin}}$