Table 3.
Summary of Pop PK Model Parameter Estimates and Bootstrap Results
| Bootstrap Value (n = 1000) | |||||
|---|---|---|---|---|---|
| Parameter | Base Model Estimates Mean %RSE | Final Model Estimates Mean (%RSE) | Mean Estimate | 5th Percentile | 95th Percentile |
| CL/F (L/h) | 11.4 | 12.6 | 12.7 | 11.8 | 13.4 |
| Power coefficient eGFR on CL/F | … | 0.52 | 0.52 | 0.49 | 0.54 |
| Power coefficient WT on CL/F | … | −0.53 | −0.53 | −0.71 | −0.35 |
| Fractional change of CL/F with Inha | … | −0.23 | −0.21 | −0.27 | −0.19 |
| Vd/F (L) | 109 | 110 | 111 | 99.8 | 120 |
| Power coefficient WT on Vd/F | … | 0.23 | 0.24 | 0.012 | 0.44 |
| D1 (h) | 0.55 | 0.58 | 0.60 | 0.39 | 0.78 |
| Dose50 (mg) | 152 | 166 | 158 | 142 | 190 |
| Dosemax (mg) | 175 | 182 | 180 | 161 | 203 |
| Interindividual variability | Mean (CV) | Mean (CV) | |||
| CL/F | 0.43 (6.2) | 0.40 (6.3) | 0.41 | 0.35 | 0.46 |
| Covariance CL/F on Vd/F | −0.21 (15.1) | −0.25 (12.7) | −0.25 | −0.32 | −0.17 |
| Vd/F | 0.46 (13.6) | 0.49 (13.1) | 0.51 | 0.37 | 0.66 |
| Covariance CL/F on D1 | 1.06 (10.2) | 1.13 (9.1) | 1.1 | 0.89 | 1.33 |
| Covariance V/F on D1 | −1.42 (12.2) | −1.51 (11.2) | −1.49 | −1.86 | −1.09 |
| D1 | 5.67 (13.4) | 5.67 (12.7) | 5.62 | 4.26 | 7.03 |
| Dose50 | 0.12 (22.8) | 0.086 (33.6) | 0.082 | 0.018 | 0.152 |
| Dosemax | 0.007 (121.2) | 0.019 (77.1) | 0.019 | 0.004 | 0.042 |
| Residual variability | Mean (%CV) | Mean (%CV) | … | … | |
| Additive | 4.88 (15.5) | 5.3 (15.1) | 5.46 | 3.41 | 8.28 |
| Proportional | 0.19 (1.3) | 0.18 (1.3) | 0.18 | 0.17 | 0.20 |
CL/F indicates total body clearance of drug from plasma following extravascular administration; %CV, percentage coefficient of variation; D1, duration of absorption; Dosemax, the highest dose at which F1 is lowest; Dose50, the dose at which F1 is 50%; eGFR, estimated glomerular filtration rate; F1, relative bioavailability; %RSE, percentage relative standard error; Vd/F, apparent central volume of distribution; WT, body weight.
a
CYP3A inhibitors coadministered.