The use of pharmacokinetics in dose individualization of factor VIII in the treatment of hemophilia A

Abstract

The pharmacokinetics of factor VIII in patients with hemophilia shows a high interpatient variability, and is affected by age, weight, level of von Willebrand factor, and blood group. A population approach to estimating individual pharmacokinetics is likely to provide the most successful strategy to tailor factor concentrate dosing to the individual needs and to ensure optimal patient outcomes, while also improving the cost-effectiveness of prophylactic replacement therapy.

Development of a Web-Accessible Population Pharmacokinetic Service—Hemophilia (WAPPS-Hemo): Study Protocol

“…All developed models and methodological issues involved in the development and validation of models are reported in separate scientific reports [14,19]. In brief, assessment of validity of a system like WAPPS-Hemo is a complex process which will be covered in a stepwise fashion.…”

Target plasma factor levels for personalized treatment in haemophilia: a Delphi consensus statement

“…Due to the need for frequent venipunctures, this was difficult for most patients, particularly young children. Today, population PK modelling using Bayesian analysis has been developed and this has resulted in less or no need for long washout periods, and has led to fewer samples required to estimate a person's FVIII/FIX PK profile . Therefore, once a specific target factor level – either trough or peak – has been selected for a patient, performing an individualized population PK assessment might allow a quicker identification of the required dose rooted on a more solid base than a fully empirical approach.…”

Cross‐sectional comparative study of pharmacokinetics and efficacy between sucrose‐formulated recombinant factor VIII (Kogenate®) and BAY 81‐8973 (Kovaltry®) in patients with severe or moderate haemophilia A in prophylaxis

“…4 In a cohort of 36 severe HA patients, the use of PKguided prophylaxis using myPKFiT ® demonstrated a decrease in ABR and AJBR, especially in patients older than 15 years. In our centre, we use extensively PopPK resources to tailor therapy, and consequently, it was also used to assess PK with rFVIII-FS, and therefore, with BAY 81-8973.…”

“…These differences disappeared with multiple dosing treatments after 6-12 months. 4 The development of different tools based on population PK (PopPK) models allows clinicians to predict the PK parameters and to tailor prophylaxis with more convenient sparse sampling. 1,2 On the other hand, BAY 81-8973 reported an improved PK profile after a single dose of 50 IU/kg compared to another rFVIII (Advate ® ) in 18 adult patients in a randomized crossover PK study.…”