Table 3.
Population PK-model parameter estimates
| Final model parameter estimates
|
Estimates from bootstrap analysisa
|
|||
|---|---|---|---|---|
| Parameter | Population mean | RSE, % | Shrinkage, % | Median (90% CI) |
| Cl/F (L/h) | 296 | 3.09 | – | 296 (283–312) |
| V2/F (L)b | 2,740 | – | – | – |
| Q/F (L/h) | 120 | 14.3 | – | 120 (91.8–173) |
| V3/F (L)b | 2,490 | – | – | – |
| KA (hours)b | 2.98 | – | – | – |
| Interindividual variability, %CV | ||||
| IIV (Cl/F) | 66.2 | 19.5 | 27.3 | 66.4 (50.2–78.1) |
| Correlation (Cl/F–V2/F) | 0.921 | 20.5 | – | 0.918 (0.881–0.931) |
| IIV (V2/F) | 113 | 21.3 | 30.5 | 113 (87.8–137) |
| IIV (KA) | 68.9 | – | 73.5 | – |
| IIV (F) | 54.0 | 22.7 | 38.0 | 53.1 (42.0–66.8) |
| IIV (RV) | 19.2 | 29.8 | 45.3 | 18.5 (13.4–23.4) |
| Residual variability, % | ||||
| PK studies | 27.8 | 5.29 | – | 27.9 (25.6–30.3) |
| Efficacy studies | 56.0 | 5.05 | – | 56.0 (51.5–60.9) |
Notes:
Nineteen runs with minimization terminated were excluded when calculating bootstrap results;
V2/F, V3/F, and KA parameters were fixed to the obtained by using plasma-concentration data from PK and safety studies. Correlation (Cl/F–V2/F) calculated as covariance (Cl/F–V2/F)/square root (variance [Cl/F] × variance [V2/F]).
Abbreviations: Cl/F, apparent clearance; CV, coefficient of variation; F, bioavailability; IIV, interindividual variability; KA, first-order absorption-rate constant; PK, pharmacokinetic; Q/F, apparent intercompartmental clearance; RSE, relative standard error; RV, residual variability; V2/F, apparent central volume of distribution; V3/F, apparent peripheral volume of distribution.