| Parameter Name | Units | INH | RIF | Ranges used for antibiotic- specific PRCC | Reference | |
|---|---|---|---|---|---|---|
| Plasma PK parameters (1) | ||||||
| Absorption rate constant (ka) | h−1 | 1–5 | 0.2–0.8 | 0.1–10 | Fit to data in [18] guided by values in [15, 57, 58] | |
| Intercompartmental clearance rate constant (Q) | L/h/kg | 0.025–0.2 | 0.1–0.7 | 0.01–1 | Fit to data in [18] guided by values in [15, 57, 58] | |
| Plasma volume of distribution (Vp) | L/kg | 0.1–2 | 0.5–1.5 | 0.05–5 | Fit to data in [18] guided by values in [15, 57, 58] | |
| Peripheral volume of distribution (other organs and tissues) (Vpe) | L/kg | 20–40 | 0.1–1 | 0.1–50 | Fit to data in [18] guided by values in [15, 57, 58] | |
| Plasma clearance rate constant (CL) | L/h/kg | 0.6–1.8 | 0.25–0.5 | 0.05–5 | Fit to data in [18] guided by values in [15, 57, 58] | |
| Lung tissue PK parameters | ||||||
| Degradation rate constant, extracellular (Kdeg,e) | s−1 | 5.5*10^-9 | 7.5*10^-8 | 1*10^-9–1*10^-7 | Fit to data in [15] | |
| Degradation rate constant, intracellular (Kdeg,i) | s−1 | 6.4*10^-3 | 6.7*10^-3 | 5*10^-4–5*10^-2 | Fit to data in [15] | |
| Effective diffusivity (D) | cm2/s | 1.1*10^-7 | 7*10^-7 | 1*10^-8–1*10^-6 | Fit to data in [15] guided by values in [75] | |
| Cellular accumulation ratio (2) (a) | - | 0.35 | 18 | 0.2–20 | Fit to data in [15] guided by values in [76–79] | |
| Vascular permeability (p) | cm/s | 8.4*10^-6 | 1*10^-5 | 1*10^-6–1*10^-4 | Fit to data in [15] guided by values in [80] | |
| Permeability coefficient (PC) | - | 0.25 | 3.3 | 0.1–10 | [15] | |
| PD parameters | ||||||
| C50 for intracellular Mtb (C50,BI) | mg/L | 0.02 | 10 | 0.01–10 | [23, 38, 39, 59] | |
| C50 for extracellular replicating Mtb (C50,be) | mg/L | 0.04 | 1.23 | 0.01–10 | [23, 38, 39, 59] | |
| C50 for extracellular non-replicating Mtb (C50,bn) | mg/L | 0.5 | 5 | 0.01–10 | [23, 38, 39, 59] | |
| Hill constant for intracellular Mtb (HBI) | - | 1 | 0.48 | 0.1–2 | [23, 38, 39, 59] | |
| Hill constant for extracellular replicating Mtb (HBE) | - | 1 | 0.7 | 0.1–2 | [23, 38, 39, 59] | |
| Hill constant for extracellular non-replicating Mtb (HBN) | - | 1 | 0.7 | 0.1–2 | Assumed same as extracellular replicating | |
| Max activity intracellular (Emax,BI) | s1 | 7.7*10^-5 | 1.1*10^-4 | 1.7*10^-5–1.5*10^-3 | Fit to data in [4] guided by values in [38, 39] | |
| Max activity extracellular (Emax,BE) | s−1 | 2.6*10-4 | 5*10^-4 | 1.7*10^-5–1.5*10^-3 | Fit to data in [4] guided by values in [38, 39] | |
(1)
Plasma PK parameters are given a range of values to account for inter-individual variation
(2)
Steady state concentration inside macrophages/concentration outside macrophages