Schematic overview of the integrated population PK model consisting of 1-compartment models described by central volume of distribution (V) and clearance (CL). The VWF activity inhibits the clearance of FVIII and is described by an I_max relationship, where IC₅₀ describes the VWF activity resulting in 50% of the maximal inhibitory effect. The change in endogenous VWF and FVIII amounts over time was described with a turnover model with zero-order production rate k_in.