Table 3. Parameter and covariate parameter estimates for the full population PK model.
| Parameter estimates and bootstrap results | ||||
|---|---|---|---|---|
| Full model | Bootstrapa | |||
| Estimates (RSE %) | IIV (RSE %) | Median (IIV %) | 95% CI (95% CI for IIV) | |
| CL/F, L/h | 20.4 (4.7) | 31.7 (3.7) | 20.2 (31.3) | 18.6, 21.8 (28.2, 34.8) |
| V/F, L | 110 (1.2) | – | 110 | 108, 113 |
| Ka, /h | 13.8 (7.9) | 198 (4.2) | 14.0 (198) | 12.1, 16.6 (180, 222) |
| Proportional error, TAD ≤ 5 hours, % | 22.9 (3.8) | 65.8 (5.5) | 22.8 (66.4) | 21.0, 24.7 (57.2, 73.1) |
| Proportional error, TAD > 5 hours, % | 52.6 (4.7) | 65.8 (5.5) | 52.5 (66.4) | 48.0, 57.3 (57.2, 73.1) |
| Lag time, h | 0.3 (0.8) | – | 0.3 | 0.3, 0.3 |
| Scaling parameter | 0.5 (9.0) | – | 0.5 | 0.4, 0.5 |
| Covariate parameter estimates | ||||
| PK parameter | Covariate | Estimate | %RSE | 95% CIa |
| CL/F, L/h | Age | –0.20 | –28.6 | –0.31, –0.08 |
| CL/Fb, L/h | BWT | 0 (FIX) | NA | 0, 0 (FIX) |
| CL/F, L/h | BCCL | 0.32 | 16.7 | 0.21, 0.42 |
| CL/F, L/h | BCRP | –0.02 | –46.0 | –0.04, 0.00 |
| CL/F, L/h | Black | 0.91 | 54.9 | 0.42, 1.78 |
| CL/F, L/h | Asian | 0.95 | 6.07 | 0.83, 1.08 |
| CL/F, L/h | Other race | 0.96 | 5.91 | 0.86, 1.12 |
| CL/F, L/h | Non-Hispanic | 1.12 | 4.75 | 1.04, 1.24 |
| CL/F, L/h | Female | 1.05 | 2.77 | 0.99, 1.11 |
| V/F, L | Age | –0.22 | –22.6 | –0.32, –0.13 |
| V/F, L | BWT | 0.68 | 8.37 | 0.55, 0.79 |
a760 in 1,000 runs minimized successfully. bEffect of BWT on CL/F was fixed to 0, and RSE and CI could not be calculated. Reference patient defined as: White, male, Hispanic, body weight 83.3 kg, age 50 years, BCRP 0.49 mg/dL, BCCL 120 mL/min. BCCL = baseline creatinine clearance; BCRP = baseline C-reactive protein; BWT = baseline body weight; CI = confidence interval; CL/F = apparent oral clearance; IIV = interindividual variability; Ka = first-order absorption rate; NA = not available; PK = pharmacokinetics; RSE = relative standard error; TAD = time after dose; V/F = apparent volume.