. 2017 Nov 9;73(2):437–447. doi: 10.1093/jac/dkx380

Table 1.

Final parameter estimates of the MTP model applied to cfu of M. tuberculosis with rifampicin, isoniazid or ethambutol in mono exposure

Parameter	Description	Estimate [RSE^a (%)]
Natural growth
k_G (days⁻¹)	growth rate of the fast-multiplying state bacteria	0.796 (5)
${k_{F S}}_{L i n}^{a, b}$ (days⁻²)	second-order time-dependent transfer rate between fast- and slow-multiplying state	0.166·10⁻² fixed^b
${k_{F N}}^{a, b}$ (days⁻¹)	first-order transfer rate between fast- and non-multiplying state	0.897·10⁻⁶ fixed
${k_{S N}}^{a, b}$ (days⁻¹)	first-order transfer rate between slow- and non-multiplying state	0.186 fixed
${k_{S F}}^{a, b}$ (days⁻¹)	first-order transfer rate between slow- and fast-multiplying state	0.0145 fixed
${k_{N S}}^{a, b}$ (days⁻¹)	first-order transfer rate between non- and slow-multiplying state	0.123·10⁻² fixed
F₀ (mL⁻¹)	initial fast-multiplying state bacterial number	209·10³ (17)
S₀ (mL⁻¹)	initial slow-multiplying state bacterial number	324·10³ (12)
Exposure–response relationships
rifampicin
${E_{m a x}}_{R}^{F G}$ (days⁻¹)	maximum achievable rifampicin-induced inhibition of fast-multiplying state growth	1 fixed
${E C}_{50}_{R I F}^{F G}$ (mg·L⁻¹)	concentration at 50% of ${E_{m a x}}_{R I F}^{F G}$	0.388 (19)
$γ_{R}^{F G}$	Hill factor drug effect	2.8 (28)
${E_{m a x}}_{R I F}^{F D}$ (days⁻¹)	maximum achievable rifampicin-induced fast-multiplying state kill rate	1.97 (3)
${E C}_{50}_{R I F}^{F D}$ (mg·L⁻¹)	concentration at 50% of ${E_{m a x}}_{R I F}^{F D}$	0.00303 (10)
${E_{m a x}}_{R I F}^{S D}$ (days⁻¹)	maximum achievable rifampicin-induced slow-multiplying state kill rate	1.79 (4)
${E C}_{50}_{R I F}^{S D}$ (mg·L⁻¹)	concentration at 50% of ${E_{m a x}}_{R I F}^{S D}$	0.0113 (32)
$k_{R I F}^{N D}$ (days⁻¹)	rifampicin linear non-multiplying state kill rate	3.29 (17)
isoniazid
${E_{m a x}}_{I N H}^{F D}$ (days⁻¹)	maximum achievable isoniazid-induced fast-multiplying state kill rate	22.2 (35)
${E C}_{50}_{I N H}^{F D}$ (mg·L⁻¹)	concentration at 50% of ${E_{m a x}}_{I N H}^{F D}$	0.168 (34)
$γ_{H}^{F D}$	Hill factor drug effect	1.9 (11)
${E_{m a x}}_{I N H}^{S D}$ (days⁻¹)	maximum achievable isoniazid-induced slow-multiplying state kill rate	8.55 (17)
${E C}_{50}_{I N H}^{S D}$ (mg·L⁻¹)	concentration at 50% of ${E_{m a x}}_{I N H}^{S D}$	0.0329 (49)
$γ_{H}^{S D}$	Hill factor drug effect	1.74 (25)
$k_{o n} (L \cdot {m g}^{- 1} \cdot d a y s)$	rate of resistance development	0.0206 (31)
$k_{o f f} (L \cdot {m g}^{- 1} \cdot d a y s)$	rate of resistance reversal	0 fixed
${k_{A R}}_{I N H}^{F D}$ (days⁻¹)	linear isoniazid adaptive resistance on fast-multiplying state kill	522 (46)
${k_{A R}}_{I N H}^{S D}$ (days⁻¹)	linear isoniazid adaptive resistance on slow-multiplying state kill	2350 (51)
ethambutol
${E_{m a x}}_{E M B}^{F D}$ (days⁻¹)	maximum achievable ethambutol-induced fast-multiplying state kill rate	2.21 (1)
${E C}_{50}_{E M B}^{F D}$ (mg·L⁻¹)	concentration at 50% of ${E_{m a x}}_{E M B}^{F D}$	0.86 (16)
$γ_{E}^{F D}$	Hill factor drug effect	2.46 (23)
$k_{E M B}^{S D}$ (days⁻¹)	ethambutol linear slow-multiplying state kill rate	4.39 (69)

RSE, relative standard error reported on the approximate standard deviation scale obtained using sampling importance resampling (SIR).¹⁵

Fixed to previously published values.²