Summary of PK parameters for rFVIIIFc and rFVIII in different mouse strains
| Mouse strain . | HemA* . | C57BL/6* . | FcRn KO* . | hFcRn transgenic (Tg32B)* . | ||||
|---|---|---|---|---|---|---|---|---|
| Treatment . | rFVIIIFc† . | rFVIII† . | rFVIIIFc† . | rFVIII† . | rFVIIIFc† . | rFVIII† . | rFVIIIFc† . | rFVIII† . |
| Cmax, mIU/mL | 2613.6 | 2710.4 | 2356.2 | 2000.1 | 2734.9 | 2458.4 | 3135.3 | 3137.0 |
| Half-life, h | 13.7 | 7.6 | 9.6 | 4.3 | 6.4 | 6.9 | 9.6 | 4.1 |
| MRT, h | 17.6 | 11.0 | 9.8 | 5.4 | 6.3 | 8.5 | 12.8 | 5.4 |
| Vss, mL/kg | 68.2 | 49.2 | 67.5 | 50.8 | 49.3 | 51.6 | 64.1 | 49.6 |
| CL, mL/h/kg | 3.9 | 4.5 | 6.9 | 9.3 | 7.8 | 6.1 | 4.1 | 7.3 |
| AUC, h × mIU/mL | 32 332.4 | 28 026.8 | 18 089.1 | 13 404.0 | 16 087.2 | 20 609.3 | 30 534.5 | 17 165.7 |
| Mouse strain . | HemA* . | C57BL/6* . | FcRn KO* . | hFcRn transgenic (Tg32B)* . | ||||
|---|---|---|---|---|---|---|---|---|
| Treatment . | rFVIIIFc† . | rFVIII† . | rFVIIIFc† . | rFVIII† . | rFVIIIFc† . | rFVIII† . | rFVIIIFc† . | rFVIII† . |
| Cmax, mIU/mL | 2613.6 | 2710.4 | 2356.2 | 2000.1 | 2734.9 | 2458.4 | 3135.3 | 3137.0 |
| Half-life, h | 13.7 | 7.6 | 9.6 | 4.3 | 6.4 | 6.9 | 9.6 | 4.1 |
| MRT, h | 17.6 | 11.0 | 9.8 | 5.4 | 6.3 | 8.5 | 12.8 | 5.4 |
| Vss, mL/kg | 68.2 | 49.2 | 67.5 | 50.8 | 49.3 | 51.6 | 64.1 | 49.6 |
| CL, mL/h/kg | 3.9 | 4.5 | 6.9 | 9.3 | 7.8 | 6.1 | 4.1 | 7.3 |
| AUC, h × mIU/mL | 32 332.4 | 28 026.8 | 18 089.1 | 13 404.0 | 16 087.2 | 20 609.3 | 30 534.5 | 17 165.7 |
Cmax indicates maximum plasma FVIII activity after infusion; KO, knockout; MRT, mean residence time; Vss, volume of distribution at steady state; CL, clearance; and AUC, area under the curve.
PK parameters of rFVIII and rFVIIIFc were compared only within the same mouse strain not across strains because the same molecule can display different t1/2 in different mouse strains.
The PK evaluation of each molecule used a cohort of 36 mice, sampled by terminal vena cava bleeding from 4 mice at each of the 9 time points. The group means at each time point were used for noncompartment modeling in WinNonLin to derive PK parameter estimates.