Table 2.
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 |
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.