Time course of rVIII-SingleChain plasma levels after coadministration with rD′D3-FP in rats and rabbits and dependency of FVIII half-life extension on molar excess of rD′D3-FP over endogenous VWF. Plasma levels of rVIII-SingleChain (antigen, dosed at 200 IU/kg in rats [A] and 150 IU/kg in rabbits [B]), alone or coadministered with increasing doses of rD′D3-FP and pdVWF (400 IU/kg in rats and 300 IU/kg in rabbits) as control. The data show the dose-dependent increase in rVIII-SingleChain plasma exposure with increased dosing of rD′D3-FP. The shorter half-life of rVIII-SingleChain coadministered with pdVWF might be explained by a shorter half-life of human VWF in a rat and rabbit model. The horizontal dashed line represents the detection limit of the assay; data are mean ± standard deviation (SD) (n = 2-3). (C) Fold increase in the terminal plasma half-life of rVIII-SingleChain as a function of the molar excess of rD′D3-FP over endogenous VWF for rats (●) and for rabbits (○). The dotted gray line represents a ratio of 1; ie, the terminal plasma half-life of rVIII-SingleChain alone.