@article{Hendrika Hazendonk_Karin Fijnvandraat_Janske Lock_Mariëtte Driessens_Felix van der Meer_Karina Meijer_Marieke Kruip_Britta Laros-van Gorkom_Marjolein Peters_Saskia de Wildt_Frank Leebeek_Marjon Cnossen_Ron Mathôt_2016, place={Pavia, Italy}, title={A population pharmacokinetic model for perioperative dosing of factor VIII in hemophilia A patients}, volume={101}, url={https://haematologica.org/article/view/7842}, DOI={10.3324/haematol.2015.136275}, abstractNote={The role of pharmacokinetic-guided dosing of factor concentrates in hemophilia is currently a subject of debate and focuses on long-term prophylactic treatment. Few data are available on its impact in the perioperative period. In this study, a population pharmacokinetic model for currently registered factor VIII concentrates was developed for severe and moderate adult and pediatric hemophilia A patients (FVIII levels <0.05 IUmL<sup>−1</sup>) undergoing elective, minor or major surgery. Retrospective data were collected on FVIII treatment, including timing and dosing, time point of FVIII sampling and all FVIII plasma concentrations achieved (trough, peak and steady state), brand of concentrate, as well as patients’ and surgical characteristics. Population pharmacokinetic modeling was performed using non-linear mixed-effects modeling. Population pharmacokinetic parameters were estimated in 75 adults undergoing 140 surgeries (median age: 48 years; median weight: 80 kg) and 44 children undergoing 58 surgeries (median age: 4.3 years; median weight: 18.5 kg). Pharmacokinetic profiles were best described by a two-compartment model. Typical values for clearance, intercompartment clearance, central and peripheral volume were 0.15 L/h/68 kg, 0.16 L/h/68 kg, 2.81 L/68 kg and 1.90 L/68 kg. Interpatient variability in clearance and central volume was 37% and 27%. Clearance decreased with increasing age (<em>P</em><0.01) and increased in cases with blood group O (26%; <em>P</em><0.01). In addition, a minor decrease in clearance was observed when a major surgical procedure was performed (7%; <em>P</em>&lt;0.01). The developed population model describes the perioperative pharmacokinetics of various FVIII concentrates, allowing individualization of perioperative FVIII therapy for severe and moderate hemophilia A patients by Bayesian adaptive dosing.}, number={10}, journal={Haematologica}, author={Hendrika Hazendonk and Karin Fijnvandraat and Janske Lock and Mariëtte Driessens and Felix van der Meer and Karina Meijer and Marieke Kruip and Britta Laros-van Gorkom and Marjolein Peters and Saskia de Wildt and Frank Leebeek and Marjon Cnossen and Ron Mathôt}, year={2016}, month={Sep.}, pages={1159-1169} }