Multidose pharmacokinetics of factor IX: implications for dosing in prophylaxis

The aim of this study was to investigate the use of single-dose pharmacokinetic data for factor IX (FIX) to predict multidose pharmacokinetics and explore their use for pharmacokinetic dosing in prophylactic treatment of haemophilia B. Eight patients with severe haemophilia B were enrolled. Using single-dose pharmacokinetic data for each patient, plasma factor IX procoagulant activity (FIX:C) curves during prophylactic dosing were computer-simulated. The simulations were verified by repeated blood sampling and measurements of FIX:C. Theoretical dosing regimens to maintain a plasma trough level of 1.0 U dL-1 of FIX:C were calculated. A 2 x 2 week cross-over study on standard dosing according to bodyweight vs. dosing every three days based on individual pharmacokinetics was carried out. FIX:C was measured during each treatment period. FIX:C data from the plasma sampling generally confirmed the single-dose pharmacokinetic data used. Pharmacokinetically tailored dosing of FIX could result in considerable savings of factor concentrate as compared to current standard dosing. The study demonstrates the applicability of individual pharmacokinetics as a tool for cost-effective utilization of FIX concentrates in the prophylactic treatment of haemophilia B.