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

Table 3.

Final parameter estimates of the GPDI model applied to cfu of M. tuberculosis with rifampicin, isoniazid and ethambutol in different combinations

PD interaction	Parameter	Estimate [RSE^a (%)]
Rifampicin/isoniazid	${I N T}_{R I F, I N H}^{F D}$	−0.679 (11)
	${I N T}_{I N H, R I F}^{F D}$	0 fixed^b
	${I N T}_{R I F, I N H}^{S D}$	1.42 (22)
	${I N T}_{I N H, R I F}^{S D}$	15.2 (49)
Isoniazid/ethambutol	${I N T}_{I N H, E M B}^{F D}$	0 fixed^b
	${I N T}_{E M B, I N H}^{F D}$	1.72 (15)
	${I N T}_{I N H, E M B}^{S D}$	164 (259)
	${I N T}_{E M B, I N H}^{S D}$	0.0963 (81)
Rifampicin/ethambutol	${I N T}_{R I F, E M B}^{F D}$	−0.99 fixed^c
	${I N T}_{E M B, R I F}^{F D}$	−0.668 (22)
	${I N T}_{R I F, E M B}^{S D}$	486 (12)
	${I N T}_{E M B, R I F}^{S D}$	2.09 (32)
Rifampicin/isoniazid/ethambutol	${I N T}_{R I F, I N H \| E M B}^{S D}$	−0.749 (18)

The PD interactions were estimated as a maximal fractional change in the exposure–response parameters EC₅₀ (Table 1) obtained for rifampicin, isoniazid or ethambutol in mono exposure. Maximal fractional change of EC₅₀ of different drugs in mono exposure as defined in Table 1. The interaction parameters INT were estimated as $1 + \frac{{I N T}_{A, B} \cdot C_{A}}{{E C}_{50}_{A, B} + C_{A}}$ . The INT value reflects the deviation from expected additivity of drug effects identified, on either/both of the F or S sub-states, in mono exposure as fractional decrease (negative value, synergism), increase (positive value, antagonism) or no increase (0 fixed, no PD interaction) in EC₅₀.

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

Fixed to 0, reflecting additivity of drug effects identified in mono exposure, i.e. no PD interaction.

Fixed to − 0.9999, reflecting a maximal decrease in EC₅₀ identified in mono exposure.