Table 3.
Pharmacokinetic data after intravenous and subcutaneous administration of AMG 108
| AMG 108 dose and route of administration | ||||
|---|---|---|---|---|
| 100 mg IV | 300 mg IV | 300 mg SC | 75 mg SC | |
| Day 1 (first dose) | (n = 12) | (n = 12) | (n = 12) | (n = 12) |
| Cmax (nM; mean (SD)) | 312 (72) | 806 (112) | 220 (58) | 26.7 (12.9) |
| Tmax (hr; median (range)) | 1.0 (0.5-24.0) | 1.0 (0.5-12.0) | 144 (144-335) | 144 (48-145) |
| AUC0-τ (nM; mean (SD)) | 2,580 (665) | 8,280 (1,690) | 4,230 (1,210) | 244 (156) |
| Trough concentration (nM; mean (SD)) | 14.9 (15.2) | 148 (48) | 96.3 (38.3) | BQL |
| Day 56 (third dose) | (n = 12) | (n = 8)a | (n = 12) | (n = 6)a |
| Cmax (nM; mean (SD)) | 315 (91) | 960 (192) | 397 (123) | 41.4 (11.1) |
| Tmax (hr; median (range)) | 0.51 (0.50-8.0) | 0.51 (0.50-8.1) | 168 (48-336) | 48 (48-169) |
| AUC0-τ (nM; mean (SD)) | 2,700 (1,360) | 12,000 (2,230) | 8,610 (3,010) | 449 (213) |
| Trough concentration (nM, mean (SD)) | 22.5 (32.3) | 257 (93) | 216 (100) | BQL |
AUC0-τ,area under the concentration-time curve, estimated by using a linear/log trapezoidal method from days 1 to 28 for the first dose and days 56 to 84 for the third dose; BQL, below the quantification limit; Cmax, maximum observed serum concentration; hr, hour; IV, intravenous; nM, nanomolar; SC, subcutaneous; SD. standard deviation; Tmax, time to Cmax. aPatients who did not receive all 3 doses of study medication were excluded from group mean for day 56.