Table 2.
Population PK parameters of BYL719 and bootstrap validation
| Lag time model | Transit model | |||||
|---|---|---|---|---|---|---|
| Parameter*† | Estimate | RSE (%) | 95% confidence interval limits† | Estimate | RSE (%) | 95% confidence interval limits‡ |
| OFV | 1969 | – | – | 1508 | – | – |
| Disposition | ||||||
| CL (l h−1) | 11.5 | 9.1 | (10.4, 12.6) | 10.1 | 4.6 | (9.28, 11.0) |
| V (l) | 118 | 4.9 | (101, 135) | 108 | 6.4 | (97.3, 120) |
| BSV CL (%) | 26.7 | 3.6 | (20.1, 34.7) | – | – | |
| BSV V (%) | 41 | 3.1 | (26.0, 50.0) | 27.6 | 24.3 | (20.8, 33.1) |
| Absorption | ||||||
| F | – | – | – | 1 (fixed) | – | – |
| Ka (1 h−1) | 0.784 | 4.3 | (0.607, 0.996) | 3.36 (fixed) | – | – |
| tlag (h) | 0.489 (fixed) | – | – | – | – | – |
| MTT (h) | – | – | – | 1.28 | 6.4 | (1.12, 1.49) |
| n | – | – | – | 8.09 | 4.6 | (6.22, 10.0) |
| BSV F (%) | – | – | – | 26.0 | 29.1 | (17.9, 32.8) |
| BOV F (%) | – | – | – | 25.3 | 20.2 | (18.1, 31.6) |
| BSV Ka (%) | 52.4 | 3.4 | (26.9, 87.4) | – | – | – |
| BOV Ka (%) | 62.8 | 3.4 | (42.9, 81.0) | – | – | – |
| BOV tlag (%) | 55.9 | 3.3 | (44.8, 67.0) | – | – | – |
| BSV MTT (%) | – | – | – | 31.6 | 41.2 | (16.3, 41.0) |
| BOV MTT (%) | – | – | – | 46.2 | 17.1 | (39.5, 52.6) |
| Residual error (%) | 36.6 | 1.5 | (31.4, 40.9) | 31.6 | 2.4 | (26.4, 36.5) |
*
PK parameters are as defined in equation 1 to 6 (Methods). BSV, between-subject variability; BOV, between-occasion variability; OFV, objective function value; RSE, relative standard error.
†
Major model building steps are provided in the Supplementary material.
‡
Calculated from 500 bootstrapped resamples.