TY - JOUR
T1 - A population pharmacokinetic model for perioperative dosing of factor VIII in hemophilia A patients
AU - Hazendonk, Hendrika
AU - Fijnvandraat, Karin
AU - Lock, Janske
AU - Driessens, Mariëtte
AU - van der Meer, Felix
AU - Meijer, Karina
AU - Kruip, Marieke
AU - Gorkom, Britta Laros-van
AU - Peters, Marjolein
AU - de Wildt, Saskia
AU - Leebeek, Frank
AU - Cnossen, Marjon
AU - Mathôt, Ron
PY - 2016
Y1 - 2016
N2 - 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(-1)) 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 (P <0.01) and increased in cases with blood group O (26%; P <0.01). In addition, a minor decrease in clearance was observed when a major surgical procedure was performed (7%; P <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
AB - 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(-1)) 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 (P <0.01) and increased in cases with blood group O (26%; P <0.01). In addition, a minor decrease in clearance was observed when a major surgical procedure was performed (7%; P <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
U2 - https://doi.org/10.3324/haematol.2015.136275
DO - https://doi.org/10.3324/haematol.2015.136275
M3 - Article
C2 - 27390359
SN - 0390-6078
VL - 101
SP - 1159
EP - 1169
JO - Haematologica
JF - Haematologica
IS - 10
ER -