rFIXFc activity PK parameters in 11 subjects with hemophilia B
| Dose, IU/kg . | n . | Cmax, IU/dL . | AUCINF, h × IU/dL . | CL, mL/h/kg . | Vss, mL/kg . | MRT, h . | t1/2α, h . | t1/2β, h . | Incremental recovery, IU/dL per IU/kg* . | C168h, IU/dL† . | Time to 1% above baseline, d‡ . | Time to 3% above baseline, d‡ . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 25 | 1 | 20.4 | 766 | 3.56 | 271 | 76.2 | 0.612 | 53.5 | 0.771 | 1.11 | 7.34 | 3.81 |
| 50 | 5 | 47.5 ± 12.9 (33.0-61.1) | 1700 ± 548 (1300-2650) | 3.44 ± 0.833 (2.05-4.18) | 262 ± 54.2 (166-296) | 77.0 ± 6.80 (67.9-85.9) | 3.31 ± 3.13 (0.130-8.15) | 57.6 ± 8.27 (47.9-67.2) | 0.870 ± 0.214 (0.633-1.12) | 2.47 ± 0.911 (1.63-3.97) | 10.1 ± 1.58 (8.41-12.4) | 6.28 ± 1.11 (5.25-8.10) |
| 100 | 5 | 98.5 ± 7.84 (90.8-110) | 4020 ± 986 (3090-5130) | 2.84 ± 0.657 (2.13-3.55) | 183 ± 27.9 (162-221) | 65.9 ± 10.3 (53.2-76.5) | 10.3 ± 5.64 (3.97-16.6) | 56.5 ± 14.1 (42.4-74.5) | 1.02 ± 0.113 (0.890-1.18) | 4.65 ± 1.73 (3.08-6.85) | 12.3 ± 2.49 (9.87-15.0) | 8.53 ± 1.58 (7.07-10.3) |
| Mean ± SD for all dose groups | 11 | NA§ | NA§ | 3.18 ± 0.745 (2.05-4.18) | 227 ± 57.1 (162-296) | 71.9 ± 9.66 (53.2-85.9) | NA§ | 56.7 ± 10.4 (42.4-74.5) | 0.930 ± 0.179 (0.633-1.18) | NA§ | NA§ | NA§ |
| Dose, IU/kg . | n . | Cmax, IU/dL . | AUCINF, h × IU/dL . | CL, mL/h/kg . | Vss, mL/kg . | MRT, h . | t1/2α, h . | t1/2β, h . | Incremental recovery, IU/dL per IU/kg* . | C168h, IU/dL† . | Time to 1% above baseline, d‡ . | Time to 3% above baseline, d‡ . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 25 | 1 | 20.4 | 766 | 3.56 | 271 | 76.2 | 0.612 | 53.5 | 0.771 | 1.11 | 7.34 | 3.81 |
| 50 | 5 | 47.5 ± 12.9 (33.0-61.1) | 1700 ± 548 (1300-2650) | 3.44 ± 0.833 (2.05-4.18) | 262 ± 54.2 (166-296) | 77.0 ± 6.80 (67.9-85.9) | 3.31 ± 3.13 (0.130-8.15) | 57.6 ± 8.27 (47.9-67.2) | 0.870 ± 0.214 (0.633-1.12) | 2.47 ± 0.911 (1.63-3.97) | 10.1 ± 1.58 (8.41-12.4) | 6.28 ± 1.11 (5.25-8.10) |
| 100 | 5 | 98.5 ± 7.84 (90.8-110) | 4020 ± 986 (3090-5130) | 2.84 ± 0.657 (2.13-3.55) | 183 ± 27.9 (162-221) | 65.9 ± 10.3 (53.2-76.5) | 10.3 ± 5.64 (3.97-16.6) | 56.5 ± 14.1 (42.4-74.5) | 1.02 ± 0.113 (0.890-1.18) | 4.65 ± 1.73 (3.08-6.85) | 12.3 ± 2.49 (9.87-15.0) | 8.53 ± 1.58 (7.07-10.3) |
| Mean ± SD for all dose groups | 11 | NA§ | NA§ | 3.18 ± 0.745 (2.05-4.18) | 227 ± 57.1 (162-296) | 71.9 ± 9.66 (53.2-85.9) | NA§ | 56.7 ± 10.4 (42.4-74.5) | 0.930 ± 0.179 (0.633-1.18) | NA§ | NA§ | NA§ |
Data are expressed as mean ± SD (range).
Cmax indicates maximum activity; AUCINF, area under the curve (time zero extrapolated to infinite time); CL, clearance; Vss, volume of distribution at steady state; MRT, mean residence time; t1/2α, distribution t1/2; and t1/2β, elimination t1/2.
Incremental recovery was calculated with observed Cmax, subtracted with pretreatment baseline value subtracted, and divided by dose.
Plasma FIX activity above baseline at 168 hours (7 days) after dose.
Model-predicted time after dose when FIX activity declined to 1% or 3% (1 or 3 IU/dL) above subject's baseline.
Data are not applicable because parameters are not dose independent; thus, the mean and SD values were not calculated across the different dose groups.