Table 4.
Pharmacokinetic Parameters of Vandetanib After a Single Dose and at Steady-State
| Parameter | Dosage Level |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 1: 50 mg/m2(n = 3) |
2: 65 mg/m2(n = 2) |
3: 85 mg/m2(n = 2) |
4: 110 mg/m2(n = 8) |
5: 145 mg/m2 (n = 7) |
||||||
| Median | Range | Median | Range | Median | Range | Median | Range | Median | Range | |
| After single dose | ||||||||||
| Cmax (ng/mL) | 84.4 | 84-87.7 | 149.5 | 106-193 | 158 | 156-160 | 264 | 189-342 | 368 | 174-636 |
| Tmax (h) | 8.3 | 7.9-12 | 8.1 | 8-8.1 | 12.2 | 12.1-12.4 | 7.6 | 2.1-12.4 | 8.5 | 6.3-12.2 |
| AUC0-24 (ng/mL·h) | 1,276 | 1,193-1,310 | 2,320 | 1,638-3,002 | 2,740 | 2,530-2,950 | 4,192 | 3,179-5,234 | 6,468 | 3,060-8,297 |
| Parameter | n = 3 | n = 3 | n = 3 | n = 15 | n = 9 | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Steady-state | ||||||||||
| Ctrough,SS (ng/mL) | 413 | 334-609 | 579 | 567-690 | 857 | 442-872 | 748 | 418-996 | 888 | 433-2,367 |
| Accumulation factor* | 9.6 | 8.5-20 | 9 | 7.6-16.6 | 8.3 | 4.8-10 | 6.5 | 4.1-10.2 | 5.5 | 2.2-13.8 |
Abbreviations: Cmax, maximum concentration; Tmax, time to maximum concentration; AUC0-24, area under concentration-time curve from 0 to 24 hours after a single dose; Ctrough, SS, mean trough concentration at steady-state; h, hour.
*
Accumulation factor stands for the ratio of mean Ctrough, SS/Ctrough after the first dose.