Plasma samples were collected pre-dose and 0.25, 0.5, 1, 3, 6, 8, 24, 48, 72, 96, and 120 h after infusion of each drug. FVIII coagulant activity (FVIII:C) was measured using the same one-stage clotting assay as follows. Plasma concentrations of BAY 94-9027 and rFVIIIFc were determined by a turbidimetric assay with the SynthaSil reagent and activated partial thromboplastin time (APTT) measured on the ACL Advance System against a calibration curve of standard human plasma. The calibration range of the procedure for both BAY 94-9027 and rFVIIIFc was 1 IU/dL (lower limit of quantitation [LLOQ]) to 80 IU/dL (upper limit of quantitation [ULOQ]). Samples above the calibration range were diluted with FVIII-deficient plasma from human donors with congenital FVIII deficiency.
The following PK parameters were assessed using non-compartmental analysis (NCA) (WinNonlin® software, version 5.3; Pharsight, Mountain View, CA, USA): AUC from time 0 to the last data point (AUClast; primary parameter); AUC; maximum concentration (Cmax); t½; CL; mean residence time (MRT); volume of distribution at steady state (Vss); and incremental recovery.
The following PK parameters were assessed using non-compartmental analysis (NCA) (WinNonlin® software, version 5.3; Pharsight, Mountain View, CA, USA): AUC from time 0 to the last data point (AUClast; primary parameter); AUC; maximum concentration (Cmax); t½; CL; mean residence time (MRT); volume of distribution at steady state (Vss); and incremental recovery.