Table 2. Parameter and covariate parameter estimates for the full population PK model.
| Parameter estimates for the final full model | ||||
| Estimate (RSE%) | 95% CI for estimatea | IIV (RSE%) | 95% CI for IIVa | |
| CL/F, L/hour | 27.1 (2.41) | 25.8, 28.5 | 28.2 (0.923) | 21.4, 34.4 |
| V/F, L | 126 (2.81) | 120, 134 | 36.6 (1.9) | 25.6, 47.0 |
| Ka/hour–1 | 3.07 (10.2) | 2.56, 3.74 | NA | NA |
| Proportional error CV, TAD < 9 hours, % | 60.2 (4.42) | 54.8, 65.3 | NA | NA |
| Proportional error CV, TAD ≥ 9 hours, % | 69.6 (6.73) | 60.4, 78.3 | NA | NA |
| Covariance, CL/F-V/F | 0.0760 (33.0) | 0.0348, 0.131 | NA | NA |
| Covariate parameter estimates | ||||
| PK parameter | Covariate | Estimateb (RSE%) | 95% CIa | |
| CL/F | Age | –0.244 (33.7) | –0.419, –0.0989 | |
| CL/F | Sex: Female (vs. male) | 0.0237 (177) | –0.0598, 0.107 | |
| CL/F | Race: Asian (vs. non-Asian) | –0.103 (31.7) | –0.164, –0.0385 | |
| CL/F | BCCL | 0.233 (34.5) | 0.0688, 0.377 | |
| CL/F | BCRP | –0.0185 (75.7) | –0.0447, 0.00881 | |
| V/F | Age | –0.230 (42.3) | –0.421, –0.0449 | |
| V/F | Body weight | 0.574 (23.1) | 0.306, 0.835 | |
BCCL = baseline creatinine clearance; BCRP = baseline C-reactive protein; CI = confidence interval; CL/F = apparent oral clearance; CV = coefficient of variation; IIV = inter-individual variance; Ka = first-order absorption rate constant; NA = not available; PK = pharmacokinetics; RSE = relative standard error; TAD = time after dose; V/F = apparent volume of distribution. The derived elimination half-life was ~ 3 hours. aPredicted by the bootstrap method. All 1,000 runs were minimized successfully. bFor continuous covariates, estimates were computed as power functions, normalized to the reference (approximate median) values in the dataset; for categorical covariates, estimates were computed as a fraction of the reference category, with one estimated coefficient for each category. Reference patient defined as: White, male, 78 kg, 40 years old, BCCL 126 mL/min, BCRP 0.851 mg/dL.