20180829_A perioperative population PK model for FIX Population pharmacokinetics of factor IX in hemophilia B patients undergoing surgery Running head: Perioperative pharmacokinetics of factor IX

Background Hemophilia B is a bleeding disorder characterized by a deficiency of coagulation factor IX (FIX). In the perioperative setting, patients receive FIX concentrates to ensure hemostasis. Although FIX is usually dosed according to body weight, under- and overdosing occurs frequently during surgery. Aim The objective was to quantify and explain the inter-patient variability of perioperatively administered plasma-derived (pd) and recombinant (r) FIX concentrates. Methods Data were collected from 118 patients (median age: 40 years (range: 0.2-90), weight: 79 kg (range: 5.3-132)) with moderate (28%) or severe hemophilia B (72%), undergoing 255 surgical procedures. Population pharmacokinetic (PK) parameters were estimated using nonlinear mixed-effect modeling in NONMEM

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