Table 2.
Parameter estimates for the final current model
| Parameter | Final model | |||
|---|---|---|---|---|
| Legacy model estimate | RSE (%) | Variability | Shrinkage | |
| CL/F (L/day) | 447 | 3.51 | – | – |
| θCL/F, strong CYP3A inhibitor | 0.18 | 6.03 | – | – |
| θCL/F, moderate CYP3A inhibitor | 0.84 | 4.24 | – | – |
| θCL/F,OATP1B3 inhibitor | 0.85 | 2.54 | – | – |
| θCL/F, GO27878 | 1.63 | 4.25 | – | – |
| V2/F (L) | 118 | 13.7 | – | – |
| θV2/F, CLL/SLL/NHL | 1.71 | 12.5 | – | – |
| θV2/F,SEX=female | 0.68 | 6.68 | – | – |
| θV2/F,GO27878 | 2.33 | 4.67 | – | – |
| Q/F (L/day) | 97.2 | 5.54 | – | – |
| V3/F (L) | 119 | 4.16 | – | – |
| ka(1/day) | 3.72 | 4.09 | – | – |
| θF1,FOOD=fasting | 0.34 | 0.97 | – | – |
| θF1,FOOD=moderate fat | 1.31 | 8.24 | – | – |
| θF1,FOOD=high fat | 1.43 | 1.3 | – | – |
| θF1,FOOD=fed | 1.23 | 4.29 | – | – |
| F1,DOSE nonlinearity (400 mg as reference) | − 0.18 | 2.38 | – | – |
| ω2CL/F | 0.15 | 9.35 | CV = 39.1% | 19.0% |
| ω2V2/F | 0.21 | 6.34 | CV = 45.3% | 27.7% |
| ω2F1 | 0.10 | 13.37 | CV = 31.2% | 28.3% |
| σ2prop | 0.22 | 1.67 | – | – |
| σ2add | 3.07 × 10–7 | 39.7 | – | – |
| t1/2 (day) | 1.05 | – | – | – |
95% CI 95% confidence interval, C3AHIB CYP3A inhibitor indicator variable, CL clearance, CL/F apparent clearance, CV coefficient of variation, F1 relative bioavailability, ka first-order absorption rate constant, OATP3HIB OATP1B3 indicator variable, Q/F apparent inter-compartmental clearance, RSE residual standard error, V2/F apparent central volume of distribution, V3/F apparent peripheral volume of distribution, ω2 inter-individual variances, σ2 residual variances