Table II.
Pharmacodynamic Parameter Estimates of Crizotinib for Biomarker Response to Tumor Growth Inhibition in Mouse Xenograft Models with H3122 NSCLC or GTL16 GC Cells Following Once Daily Oral Administration
| Study | Model | EC 50 | ET 50 | E max | E 0 | k e0 | k tg | k td | T ss |
|---|---|---|---|---|---|---|---|---|---|
| ng/mL | h −1 | h −1 | h −1 | h −1 | |||||
| ALK-2 | IV | 255 (22) | – | 1 (fixed) | – | – | 0.0126 (0.0008) | 0.00115 (0.000003) | 1410 (155) |
| VI | – | 1.03 (0.023) | 1 (fixed) | 1 (fixed) | 0.030a (fixed) | 0.0126a (0.0008) | 0.00115a (0.000003) | 1410a (155) | |
| MET-2 | III | 213 (123) | – | 1 (fixed) | – | – | 0.0130 (0.0021) | 0.00672 (0.00243) | – |
| V | – | 15.8 (1.2) | 1 (fixed) | 1 (fixed) | 0.135a (fixed) | 0.0130a (0.0021) | 0.00672a (0.00243) | – |
Precision of the estimates is expressed as S.E. in parentheses. –, not applicable
Study ALK-2: athymic nu/nu mice bearing H3122 NSCLC xenografts; Study MET-2: athymic nu/nu mice bearing GTL16 GC xenografts
Results are cited from previous reports (21,22)
aThe values were estimated by the corresponding link and drug-disease models