Table 3.
Pharmacokinetics of Erlotinib and Crizotinib When Given in Combination at Two Crizotinib Dose Levels
| Geometric Mean (% CV) | ||||||
|---|---|---|---|---|---|---|
| Pharmacokinentic Parameter | Dose Level 1 (n = 7) |
Dose Level −1 (n = 19) |
||||
| Day −1a | Cycle 1, Day 1 | Cycle 1, Day 15b | Day −1a | Cycle 1, Day 1 | Cycle 1, Day 15c | |
| Erlotinib | ||||||
| Tmax, d h | 2.0 (1.0–5.0) | 4.0 (0.7–12.0) | 3.1 (1.0–6.1) | 3.0 (0.5–5.0) | 4.0 (0.6–12.0) | 3.0 (2.0–25.2) |
| Cmax, ng/mL | 1593 (26) | 1452 (21) | 2546 (24) | 1797 (36) | 1723 (38) | 2346 (43) |
| AUCτ, ng·h/mL | 23,490 (31) | 26,520 (25) | 41,770 (27) | 26,880 (39) | 30,040 (39) | 38,910 (49) |
| Crizotinib | ||||||
| Tmax d h | NA | 3.5 (1.0–6.0) | 2.0 (0.6–8.0) | NA | 4.0 (0.6–8.1) | 4.5 (0.5–6.0) |
| Cmax, ng/mL | NA | 86.8 (37) | 251.0 (46) | NA | 65.3 (50) | 185.9 (40) |
| AUCτ, ng·h/mL | NA | 581.9 (49) | 2274 (43) | NA | 400.3 (40) | 1720 (40) |
Note: Dose level of 1: crizotinib, 150 mg twice daily, plus erlotinib, 100 mg once daily. Dose level of 1: crizotinib, 200 mg twice daily, plus erlotinib, 100 mg once daily.
a
Erlotinib administered alone.
b
n = 5.
c
n = 14.
d
Presented as median (range).
CV, coefficient of variation; Tmax, time to maximum plasma concentration; Cmax, maximum concentration; AUCτ, area under the concentration-time curve over the dosing interval (crizotinib, 12 hours; erlotinib, 24 hours); NA, not applicable.