Table 2.
Fitted parameters in the final model
| Parameter | Abbreviation | Units | Population mean (%CV) | Variability* SD (%CV) |
|---|---|---|---|---|
| Systemic clearance | CL | l h−1 | 44.9 (3.1) | 0.139 (26.4) |
| Volume of central plasma compartment | V1 | l | 11.3 (6.7) | 0.147 (93.1) |
| Intercompartmental clearance | Q1 | l h−1 | 25.6 (8.9) | 0.172 (128) |
| Volume of peripheral PK compartment | V2 | l | 19 (4.4) | 0 (fixed) |
| Intercompartmental clearance | Q2 | l h−1 | 8.23 (6.4) | 0.184 (60.6) |
| Volume of peripheral PK compartment | V3 | l | 71.5 (6.8) | 0.165 (56.1) |
| Bioavailability after inhalation with concomitant charcoal treatment expressed as odds | BIO | – | 1.11 (18) | 0.452 (56.9) |
| Parameter related to fraction of dose with slow absorption | Rslow | – | 6.48 (8.1) | 0.231 (29.8) |
| Parameter related to fraction of dose with intermediate absorption | Rmed | – | 0.734 (16.8) | 0.355 (55.1) |
| Inferred absolute oral bioavailability | FORAL | – | 0.082 (15.2) | 0.329 (53.9) |
| Slow lung absorption rate | Kslow | h−1 | 0.009 (10.1) | 0.178 (57.6) |
| Intermediate lung absorption rate | Kmed | h−1 | 1.54 (20.9) | 0.455 (93.2) |
| GI tract absorption rate | KGI | h−1 | 0.34 (8.2) | 0.14 (138.1) |
| Residual error (SD) | – | – | 0.148 (3.5) | – |
Estimates were obtained by fitting the model to the plasma profiles. Provided values are population estimates (%CV).
*
Reported variabilities are unitless standard deviations of multiplicative exponential random effects. CV, coefficient of variation; GI, gastrointestinal; PK, pharmacokinetic.