Table 2.
Population pharmacokinetic parameters of the final population pharmacokinetic model
| Parameter | Estimate (%RSE) | Bootstrap estimate [n = 1000] (95% CI) |
|---|---|---|
| Population parameters | ||
| Tlag [h] | 1.64 (1.6) | 1.63 (1.56–1.70) |
| Ka [/h] | 3.38 (11) | 3.35 (2.53–4.44) |
| CL/Fpop [L/h] | 4.47 (7.6) | 4.47 (3.63–5.39) |
| V1/Fpop [L] | 136 (3.4) | 136 (126–146) |
| Q/Fpop [L/h] | 10.0 (4.5) | 10.0 (9.10–11.0) |
| V2/Fpop [L] | 1172 (11) | 1169 (875–1523) |
| Covariate effectsa | ||
| WT on CL/F | 0.75 FIX | – |
| WT on V1/F | 1 FIX | – |
| AGE on V1/F | − 0.42 (30) | − 0.43 (− 0.67 to − 0.20) |
| WT on Q/F | 0.75 FIX | – |
| WT on V2/F | 1 FIX | |
| Interindividual variability | ||
| ωTlag | 0.1 FIX | 0.1 FIX |
| ωKa | 0.672 (14) | 0.604 (0.355–0.850) |
| ωCL/F | 0.625 (8.6) | 0.627 (0.519–0.724) |
| ωV1/F | 0.297 (9.2) | 0.291 (0.220–0.379) |
| ωQ/F | 0.343 (11) | 0.344 (0.236–0.445) |
| ωV2/F | 0.779 (11) | 0.743 (0.436–0.976) |
| Residual variability | ||
| Proportional errorb | 0.165 (4.9) | 0.169 (0.144–0.199) |
AGE age in years, CI confidence interval, CL/F apparent clearance, CL/Fpop population value for CL/F for a person with a body weight of 70 kg, Ka absorption constant, Q/F apparent intercompartmental clearance, Q/Fpop population value for Q/F for a person with a body weight of 70 kg, Tlag absorption lag time, V1/F apparent volume of distribution of the central compartment, V1/Fpop population value for V1/F for a person with a body weight of 70 kg and aged 44.3 years, V2/F apparent volume of distribution of the peripheral compartment, V2/Fpop population value for V1/F for a person with a body weight of 70 kg, WT total body weight in kilograms, ω standard deviation of the interindividual variability parameter, %RSE percentage relative standard error
aCovariate parameter relationships: CL/F = CL/Fpop × (WT/70)0.75. V1/F = V1/Fpop × (WT/70) × (AGE/44.3)−0.42. Q/F = Q/Fpop × (WT/70)0.75. V2/F = V2/Fpop × (WT/70)
bResidual proportional error shown as the standard deviation