TABLE 3.
Final population pharmacokinetic model estimates
| Parameter | Estimate | RSE (%) | 95% CI | Shrinkage (%) |
|---|---|---|---|---|
| Structural model | ||||
| θCL investigation (L h−1) | 535 | 6.2 | [470–600] | |
| θCL support (L h−1) | 400 | 7.4 | [342–458] | |
| ωCL investigation (SD) | 0.068 | 16.5 | [0.176–0.344] | 44.3 |
| ωCL support (SD) | 0.195 | 9.8 | [0.357–0.527] | 40.1 |
| θQ (L h−1) | 1690 | 20.3 | [1018–2362] | |
| ωQ (SD) | 0.715 | 19.3 | [0.526–1.164] | 52.4 |
| θVc (L) | 1960 | 21.7 | [1125–2795] | |
| ωVc (SD) | 1.18 | 16.1 | [0.745–1.435] | 40.3 |
| θVp (L) | 3900 | 15.7 | [2700–5100] | |
| ωVp (SD) | 0.508 | 19.5 | [0.441–0.985] | 38.8 |
| θka (h−1) | 2.5 (fixed) | |||
| σ (SD) | 0.085 | 5.5 | [0.067–0.103] | 13.9 |
| Covariate model | ||||
| θSLCO1B1 521TC | −0.402 | 15.2 | [−0.522–−0.282] | |
| θSLCO1B1 521CC | −0.041 | 469.7 | [−0.422–0.339] |
Clearances and volumes of distribution are apparent parameters.
Abbreviations: CI, confidence interval; CL, clearance; ka, absorption rate constant; Q, inter‐compartmental clearance; RSE, relative standard error; VC, central volume of distribution; VP, peripheral volume of distribution; θ, fixed effect; σ, random effect (residual variability); ω, random effect (between‐subject variability).
In the investigation cohort: CL/F = θCL × (1 + θSLCO1B1), where θSLCO1B1 is 0 for 521TT individuals.