Table III.
Gefitinib Pharmacokinetic Parameter Estimation and Precision (CV%) in Mouse Plasma and Tissues Using the Proposed PBPK Model
| Organs | Parameters | NCA estimated | PBPK estimated | CV% | 95% CI, lower endpoint | 95% CI, upper endpoint | Diff% |
|---|---|---|---|---|---|---|---|
| Lung | K lu | 21.0 | 16.8 | 14.9 | 11.8 | 21.8 | 20.1 |
| Spleen | K s | 10.3 | 9.19 | 14.0 | 6.62 | 11.8 | 11.0 |
| Gut | K g | 9.48 | 8.64 | 13.6 | 6.29 | 11.0 | 8.87 |
| Liver | K l | 15.6 | 40.5 | 32.3 | 14.3 | 66.6 | 160 |
| CLint,H (mL/h) | 4430 | 5090 | 30.9 | 1950 | 8240 | 15.0 | |
| Kidney | K k | 8.68 | 6.49 | 13.6 | 4.73 | 8.25 | 25.2 |
| Brain | K b | 0.74 | 0.71 | 15.9 | 0.48 | 0.93 | 4.23 |
| Eye | K e | 1.40 | 0.97 | 15.1 | 0.68 | 1.27 | 30.7 |
| Heart | K h | 3.06 | 2.39 | 15.3 | 1.65 | 3.12 | 22.1 |
| Muscle | K m | 1.78 | 1.28 | 14.5 | 0.91 | 1.66 | 27.9 |
| Fat | K f | 2.03 | 1.36 | 15.4 | 0.94 | 1.78 | 33.1 |
| PSf (mL/h) | 112 | 62.6 | −28.4 | 253 | |||
| K ISF,f | 17.0 | 123 | −25.0 | 59.0 | |||
| Skin | K sk | 2.66 | 1.93 | 15.2 | 1.34 | 2.52 | 27.5 |
| PSsk (mL/h) | 512 | 262 | −2120 | 3190 | |||
| K ISF,sk | 10.1 | 222 | −34.8 | 55.1 | |||
| Remainder | K r | 8.28 | 70.6 | −3.41 | 20.0 | ||
| PSr (mL/h) | 23.5 | 36.4 | 6.41 | 40.6 | |||
| K ISF,r | 90.9 | 22.5 | 49.9 | 132 |
NCA noncompartmental analysis, PBPK physiologically based pharmacokinetic, CV coefficient of variation, 95% CI 95% confidence interval, Diff% percentage of difference