Population pharmacokinetics of the von Willebrand factor–factor VIII interaction in patients with von Willebrand disease

Abstract Recent studies have reported that patients with von Willebrand disease treated perioperatively a factor (VWF)/factor VIII (FVIII) concentrate ratio of 2.4:1 (Humate P/Haemate P) often present VWF and/or FVIII levels outside prespecified target necessary to prevent bleeding. Pharmacokinetic (PK)-guided dosing may resolve this problem. As clinical guidelines increasingly recommend aiming for certain both and FVIII, application an integrated population PK model describing activity (VWF:Act) improve quality care. In total, 695 VWF:Act 894 level measurements from 118 (174 surgeries) who were the VWF/FVIII used develop using nonlinear mixed-effects modeling. analyzed simultaneously turnover model. The protective effect on clearance was described inhibitory maximum function. An average perioperative 1.23 IU/mL decreased 460 mL/h 264 mL/h, increased half-life 6.6 11.4 hours. Clearly, in presence VWF, concomitant increase half-life, clarifying higher observed after repetitive concentrate. during treatment adequately by newly developed Clinical facilitate more accurate targeting specific P).