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Influence of blood group and von Willebrand factor on population pharmacokinetics and dose individualization of recombinant factor VIII in Taiwanese patients with haemophilia A.
- Source :
-
Haemophilia . Mar2022, Vol. 28 Issue 2, p230-238. 9p. 5 Charts, 2 Graphs. - Publication Year :
- 2022
-
Abstract
- Introduction: The large interpatient variability in the pharmacokinetic (PK) parameters of recombinant Factor VIII (rFVIII) observed in haemophilia A hinders efficient and cost‐beneficial prophylactic regimen initiation. Identification of factors influencing the PK of rFVIII may shed more light on personalised treatment. Aim: This study aimed to develop a population PK model in the Taiwanese haemophilia A and evaluate the current national health insurance (NHI) reimbursement guidelines of Taiwan for haemophilia treatment. Methods: A population PK analysis was established based on 69 Taiwanese with moderate or severe haemophilia A. A nonlinear mixed‐effects modelling (NONMEM®) was used to estimate PK parameters and their variabilities. A Monte Carlo simulation was performed to evaluate different prophylactic regimens. Results: A two‐compartment model with first‐order elimination best described the rFVIII data. Weight‐based allometric scaling was related to clearance and central volume of distribution. Blood type and baseline von Willebrand factor (VWF) were significant covariates for clearance. For single dose simulations, a time achieving target level (> 1 IU/dL) was associated with increasing rFVIII dose and VWF level. The multiple dose simulations showed that > 96.4% of patients with high VWF level (> 200%) had predicted trough level > 1 IU/dL for all dosing regimens (15‐40 IU/kg, two to three times weekly). However, for twice weekly dosing, lower percentage (47.62‐62.20%) of patients with blood group O and low VWF level (< 50%) achieved a predicted trough level > 1 IU/dL. Conclusion: The population PK of rFVIII was successfully developed. Dose adjustment based on blood type and VWF level should be considered. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 13518216
- Volume :
- 28
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Haemophilia
- Publication Type :
- Academic Journal
- Accession number :
- 155694676
- Full Text :
- https://doi.org/10.1111/hae.14493