Table 2.
Final Model Parameter Estimates
| Daclatasvir | ||||
|---|---|---|---|---|
| Parametera | Symbol | Estimateb | Standard Error (RSE%)c | 95% Confidence Intervald |
| Fixed effects | ||||
| CL/F (L/h) | θ1 | 5.29 | 0.161 (3.04) | 4.98‐5.59 |
| V/F (L) | θ2 | 64.2 | 2.04 (3.18) | 60.1‐68.2 |
| Ka (h‐1) | θ3 | 0.865 | 0.0516 (5.97) | 0.753‐0.974 |
| CL/F ∼SEX | θ6 | ‐0.110 | 0.0274 (24.9) | ‐0.197 to ‐0.053 |
| CL/F ∼TX | θ8 | ‐0.122 | 0.0336 (27.5) | ‐0.189‐0.132 |
| CL/F ∼BCRCL | θ10 | 0.235 | 0.0462 (19.7) | 0.142‐0.333 |
| V/F ∼BBWT | θ14 | 0.605 | 0.0989 (16.3) | 0.405‐0.974 |
| Random effects | ||||
| CL/F | ω1,1 | 0.155 (0.394) | 0.0157 (10.1) | 0.0176‐0.182 |
| V/F | ω2,2 | 0.145 (0.381) | 0.0216 (14.9) | 0.0168‐0.186 |
| Ka | ω3,3 | 0.756 (0.869) | 0.105 (13.9) | 0.590‐0.968 |
| CL/F: V/F | ω1,2 | 0.141 (0.941) | 0.0161 (11.4) | 0.00099‐0.171 |
| σ | ω4,4 | 0.107 (0.327) | 0.0193 (18.0) | 0.072‐0.148 |
| Residual error | ||||
| σ | θ4 | 0.375 | 0.0102 (2.72) | 0.358‐0.408 |
| Asunaprevir | ||||
|---|---|---|---|---|
| Parametera | Symbol | Estimateb | Standard Error (RSE%)c | 95% Confidence Intervald |
| Fixed effects | ||||
| CL/F (L/h) | θ1 | 52.1 | 7.35 (14.1) | 42.1‐66.8 |
| V/F (L) | θ2 | 75.1 | 13.5 (18.0) | 56.7‐101.0 |
| Ka (h‐1) | θ3 | 0.228 | 0.00395 (1.73) | 0.221‐0.234 |
| CL/F ∼BAST | θ7 | ‐0.598 | 0.0565 (9.45) | ‐0.707 to ‐0.486 |
| CL/F ∼AST | θ8 | ‐0.382 | 0.0443 (11.6) | ‐0.458 to ‐0.303 |
| F ∼FORM | θ10 | ‐0.314 | 0.144 (45.9) | ‐0.551 to ‐0.0922 |
| CL/F ∼CIRRHOSIS | θ11 | ‐0.428 | 0.140 (32.7) | ‐0.753 to ‐0.146 |
| Random effects | ||||
| CL/F | ω1,1 | 0.172 (0.415) | 0.0232 (13.5) | 0.127‐0.213 |
| V/F | ω2,2 | 0.872 (0.934) | 0.139 (15.9) | 0.663‐1.10 |
| σ | ω4,4 | 0.0672 (0.259) | 0.0176 (26.2) | 0.0364‐0.0974 |
| Residual error | ||||
| σ | θ4 | 0.68 | 0.0193 (2.84) | 0.648‐0.713 |
AST, aspartate aminotransferase at each time; BAST, baseline aspartate aminotransferase; BBWT, baseline body weight; BCRCL, baseline creatinine clearance; CIRRHOSIS, cirrhosis (yes vs no); CL/F, apparent clearance; FORM, formulation (phase 2 film‐coated tablet vs phase 3 soft‐gel capsule); Ka, absorption rate constant; TX, treatment description; V/F, apparent volume of distribution of central compartment; σ, parameters for additive residual error.
Random effects and residual error parameter estimates are shown as variance (standard deviation) for diagonal elements (ωi,i or ωi,i) and covariance (correlation) for off‐diagonal elements (ωi,j or ωi,j).
RSE, relative standard error (standard error as a percentage of estimate).
All confidence intervals are from a 500 bootstrap run.