Table 6.
Population PK parameter estimates for erlotinib and OSI-420
| Model Term | Base model (n=26) | Covariate model (LBM, n=26) | ||
|---|---|---|---|---|
| Estimate (CV %) | Bootstrap median (95% CI) |
Estimate (CV %) | Bootstrap median (95% CI) |
|
| OBJ | 968.48 | -- | 963.26 | -- |
| θKa (h−1) | 1.04 | -- | 1.04 | -- |
| θCL (L/h) | 6.22 (8.5) | 6.24 (4.72, 8.11) | 6.4 (9.0) | 6.37 (4.99, 8.09) |
| θV1 (L) | 284 (15.7) | 275.00 (193.00, 448.05) | 283 (37.1) 2 | 74.00 (195.00, 447.03) |
| θFM | 1.41 (12.8) | 1.22 (0.47, 3.33) | 0.88 (26.4) | 1.03 (0.23, 3.49) |
| θCLM (L/h) | 21.5 (8.9) | 23.60 (4.76, 47.91) | 32.6 (10.4) | 27.80 (4.04, 55.60) |
| θV2 (L) | 7.18 (62.8) | 7.67 (0.09, 21.91) | 11.6 (12.1) | 8.99 (0.04, 26.11) |
| Shared ETA scale factor, θSE |
3.46 (37.0) | 3.18 (−148.10, 16.11) | 5.96 (56.5) | 6.42 (2.29, 577.30) |
| θLBM | -- | -- | 1.71 (27.8) | 1.75 (0.69, 3.08) |
| IIVCL | 0.06 (80.8) | 0.24 (0.005, 0.44) | 0.02 (127.1) | 0.13 (0.001, 0.35) |
| IIV V1 | 0.92 (50.5) | 0.90 (0.40, 1.33) | 0.95 (50.7) | 0.92 (0.43, 1.37) |
| IOV CL | 0.38 (55.5) | 0.58 (0.29, 0.89) | 0.30 (67.9) | 0.51 (0.15, 0.85) |
| Residual error for erlotinib, ε1 |
1.2 (37.2) | 1.08 (0.66, 1.47) | 1.2 (37.1) | 1.07 (0.65, 1.48) |
| Residual error for OSI-420, ε2 |
0.78 (23.3) | 0.87 (0.37, 1.06) | 0.78 (24.2) | 0.87 (0.67, 1.06) |
OBJ, objective function value; LBM, lean body mass; IIV, inter-individual variability; IOV, inter-occasion variability; CV%, standard error of estimate expressed as coefficient of variation (%); The shared eta scale factor was estimated as described in the text. IIV, IOV and residual errors are expressed as variances.