Pharmacokinetic parameters of glycoPEGylated FVIII conjugates after intravenous administration of 280 U/kg to FVIII- and VWF-deficient mice
| Mice . | Compound . | Pharmacokinetic parameters* . | ||
|---|---|---|---|---|
| t1/2 (h) . | CL (mL/kg per h) . | MRT (h) . | ||
| FVIII-deficient mice | FVIII | 6.8 | 8.1 | 9.7 |
| 10-kDa PEG-FVIII | 10 | 8.5 | 16 | |
| 20-kDa PEG-FVIII | 14 | 3.4 | 20 | |
| 40-kDa PEG-FVIII | 14 | 3.5 | 19 | |
| 80-kDa PEG-FVIII | 15 | 6.4 | 21 | |
| VWF-deficient mice | FVIII | 0.3 | 282 | 0.3 |
| 10-kDa PEG-FVIII | 2.7 | 52 | 2.5 | |
| 20-kDa PEG-FVIII | 1.9 | 42 | 2.7 | |
| 40-kDa PEG-FVIII | 7.0 | 14 | 8.4 | |
| 80-kDa PEG-FVIII | 6.7 | 12 | 9.2 | |
| Mice . | Compound . | Pharmacokinetic parameters* . | ||
|---|---|---|---|---|
| t1/2 (h) . | CL (mL/kg per h) . | MRT (h) . | ||
| FVIII-deficient mice | FVIII | 6.8 | 8.1 | 9.7 |
| 10-kDa PEG-FVIII | 10 | 8.5 | 16 | |
| 20-kDa PEG-FVIII | 14 | 3.4 | 20 | |
| 40-kDa PEG-FVIII | 14 | 3.5 | 19 | |
| 80-kDa PEG-FVIII | 15 | 6.4 | 21 | |
| VWF-deficient mice | FVIII | 0.3 | 282 | 0.3 |
| 10-kDa PEG-FVIII | 2.7 | 52 | 2.5 | |
| 20-kDa PEG-FVIII | 1.9 | 42 | 2.7 | |
| 40-kDa PEG-FVIII | 7.0 | 14 | 8.4 | |
| 80-kDa PEG-FVIII | 6.7 | 12 | 9.2 | |
Values are based on analysis of FVIII activity in a chromogenic assay (FVIII-deficient mice) or antigen (VWF-deficient mice).